New copolymers graft of α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide obtained from atom transfer radical polymerization as vector for gene delivery

2012

Abstract New cationic α,β-poly(N-2-hydroxyethyl)- d , l -aspartamide (PHEA) graft copolymers were synthesized by ATRP, using diethylamino ethyl methacrylate (DEAEMA) as monomer for polymerization, yielding polycations (PHEA-pDEAEMA) able to condense DNA. Then, consecutive ATRP conditions were set up on PHEA-pDEAEMA to obtain copolymers containing also hydrophilic chains (PHEA-IB-pDMAEMA-pPEGMA) able to improve biocompatibility of polyplexes and to provide them stealth properties. Agarose gel studies showed that the copolymers effectively condensed plasmid DNA to form polyplexes. Light scattering studies were used to analyze the size and the ζ -potential of these polyplexes, showing that cop…

Viscosimetric investigation of the interaction between sodium dodecylsulfate micelles and a polymer drug carrier

1993

Abstract The viscosities of aqueous sodium dodecyl sulfate solutions with and without α,β-poly( N -hydroxyethyl)- dl -aspartamide (PHEA), at 15, 25 and 35°C are reported. The viscosities of SDS and of PHEA aqueous solutions are discussed in terms of the parameter D [D = ( η η 0 − 1)/φ] describing the non-ideal behavior of SDS micelles and of PHEA macromolecules. The viscosities of SDS plus PHEA aqueous solutions, discussed in terms of the parameter F [ F = η rel ( PHEA ) + η rel ( SDS ) − η rel ( SDS + PHEA )] M , demonstrate the occurrence of interactions between SDS micelles and the PHEA macromolecule. Both D and F are scarcely influenced by temperature variation.

Novel inulin-based mucoadhesive micelles loaded with corticosteroids as potential transcorneal permeation enhancers

2017

In this work a new copolymer of inulin (INU) derivatized with ethylendiamine (EDA) and retinoic acid (RA), named INU-EDA-RA, was synthetized, characterized and employed to produce micelles as carriers for topical administration of corticosteroids for the potential treatment of diseases of posterior eye segment. Spectroscopic analysis confirmed a molar derivatization degree of 11.30 and 4.30% in EDA and RA, respectively. INU-EDA-RA micelles are capable of strong mucoadhesive interactions which result time-independent and stable over time but concentration depending. Moreover micelles are able to encapsulate efficiently from 3 to 13% (w/w) of lipophilic drugs, as dexamethasone, triamcinolone …

Reaction of α,β-poly(N-hydroxyethyl)-DL-aspartamide with derivatives of carboxylic acids

1987

Lipid nanocarriers containing esters prodrugs of Flurbiprofen. Preparation, physical-chemical characterization and biological studies.

2013

In this paper, the preparation, chemical-physical, technological and in vitro characterization of nanostructured lipid carriers (NLC) carrying R-flurbiprofen ester prodrugs, were analyzed for a potential pharmaceutical application. R-flurbiprofen was chosen as a model drug because it has been found to play an effective role in counteracting secretases involved in neurodegenerative diseases, although it does not cross the Blood Brain Barrier (BBB). In this study, two R-flurbiprofen ester prodrugs (ethyl and hexyl) were successfully synthesized and entrapped into non-pegylated and pegylated NLC. The obtained systems showed average diameters in the colloidal size range, negative zeta potential…

In situ forming hydrogels of new amino hyaluronic acid/benzoyl-cysteine derivatives as potential scaffolds for cartilage regeneration

2012

A new chemical strategy is described to link ethylenediamino (EDA) groups to primary hydroxyl groups of hyaluronic acid (HA) and the obtained derivatives have been characterized by 1H-NMR and 13C-NMR analyses. Such HA–EDA derivatives have been exploited to control the functionalization degree in benzoyl-cysteine (BC) groups, chosen as moieties able to allow both self-assembling in aqueous media and an oxidative crosslinking. In particular, the kinetics of oxidation of thiol groups in HA–EDA–BC derivatives has been studied in Dulbecco's Phosphate Buffer Solution (DPBS) pH 7.4 by colorimetric assays and rheological measurements. Mechanical properties of chemical hydrogels obtained after oxida…

New hydrogel matrices based on chemical crosslinked α,β -polyas parthydrazide: Synthesis, characterization and in vivo biocompatibility studies

1996

New swellable micromatrices of α,β-polyasparthydrazide (PAHy) crosslinked with glutaraldehyde were prepared. The effect of crosslinking agent concentration was evaluated. In particular, crosslinking density affected aqueous dynamic swelling and glass-transition temperature of the material. The structure of prepared networks was also studied by scanning electron microscopy and X-ray analysis. Finally, biocompatibility of PAHy derivatives was investigated in vivo by subcutaneous implantation and in oral administration to laboratory animals.

Fluorinated and pegylated polyaspartamide derivatives to increase solubility and efficacy of Flutamide

2012

New fluorinated amphiphilic copolymers based on a biocompatible polyaspartamide have been prepared in order to obtain polymeric micelles useful for delivering anticancer drugs. In particular, α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) has been derivatized with polyethylene glycol (PEG(2000)) and ethylendiamine (EDA). Both these portions form the hydrophilic part of the copolymer, while the hydrophobic moiety is given by 1,2,4-oxadiazoles: 5-pentafluorophenyl-3-perfluoroheptyl-1,2,4-oxadiazole (PPOX) or 3-carboxyethyl-5-pentadecafluoroheptyl-1,2,4-oxadiazole (CPOX). Copolymers named PHEA-PEG(2000)-EDA-PPOX and PHEA-PEG(2000)-EDA-CPOX have been prepared with various degrees of derivati…

pH-sensitive hydrogel based on a novel photocross-linkable copolymer.

2004

A pH sensitive hydrogel has been prepared by a UV irradiation technique. Starting polymer was the PHM (poly hydroxyethylaspartamide methacrylated) obtained from polyaspartamide (PHEA) partially derivatized with methacrylic anhydride (MA). This new copolymer has been further derivatized with succinic anhydride (SA) to obtain PHM-SA that has been cross-linked by UV irradiation to form a pH sensitive hydrogel. The network, recovered after washing as a powder, has been been characterized by FT-IR spectrophotometry and particle size distribution analysis. Moreover, to have information about water affinity of the prepared sample, swelling measurements have been carried out in aqueous media mimick…

Core-Shell Arginine-Containing Chitosan Microparticles for Enhanced Transcorneal Permeation of Drugs

2019

Chitosan oligosaccharide (C) was functionalized with L-arginine (A) and short hydrocarbon chains (C-8) to design an amphiphilic copolymer, henceforth CAC(8), leading to microparticles (MPs) consisting of an arginine-decorated hydrophilic shell and inner hydrophobic domains allowing the encapsulation of high amount hydrophobic drugs such as sorafenib tosylate (>10% w/w). L-arginine side chains were selected in order to impart the final MPs enhanced transcorneal penetration properties, thus overcoming the typical biological barriers which hamper the absorption of drugs upon topical ocular administration. The mucoadhesive properties and drug release profile of the CAC(8) MPs (CAC(8)-MPs) were …

PEGYLATED POLYASPARTAMIDE–POLYLACTIDE BASED NANOPARTICLES PENETRATING CYSTIC FIBROSIS ARTIFICIAL MUCUS

2016

Here, the preparation of mucus-penetrating nanoparticles for pulmonary administration of ibuprofen in patients with cystic fibrosis is described. A fluorescent derivative of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide is synthesized by derivatization with rhodamine, polylactide, and poly(ethylene glycol), to obtain polyaspartamide− polylactide derivatives with different degrees of pegylation. Starting from these copolymers, fluorescent nanoparticles with different poly(ethylene glycol) content, empty and loaded with ibuprofen, showed spherical shape, colloidal size, slightly negative ζ potential, and biocompatibility toward human bronchial epithelial cells. The high surface poly(ethylene gly…

Amoxicillin-loaded polyethylcyanoacrylate nanoparticles: influence of PEG coating on the particle size, drug release rate and phagocytic uptake.

2001

Polyethyleneglycol (PEG)-coated polyethylcyanoacrylate (PECA) nanoparticles loaded with amoxicillin were prepared and the influence of the PEG coating on the particle size, zeta potential, drug release rate and phagocytic uptake by murine macrophages was studied. Experimental results show that this colloidal drug delivery system could be useful for intravenous or oral administration. The profile of amoxicillin release from PECA nanoparticles system was studied under various conditions similar to those of some corporeal fluids. In all these experiments, amoxicillin release in the free form was studied by HPLC analysis. Experimental results showed that at pH 7.4 drug release rises when molecu…

Preparation of Polymeric Nanoparticles by Photo-Crosslinking of an Acryloylated Polyaspartamide in w/o Microemulsion

2004

Biodegradable polymeric nanoparticles have been prepared by UV irradiation of an acryloylated water soluble polymer by an inverse microemulsion. The starting polymer was a α,β‐poly(N‐2‐hydroxyethyl)‐D,L‐aspartamide (PHEA) partially functionalized with glycidyl methacrylate (GMA) in order to introduce reactive vinyl groups in the side chain. The PHEA‐GMA copolymer obtained (PHG) was crosslinked by UV irradiation of the inverse microemulsion prepared by mixing an aqueous solution of PHG with propylene carbonate (PC)/ethyl acetate (EtOAc) in the presence of sorbitan trioleate (SPAN 85) as surfactant. Nanoparticles obtained were characterized by FTIR spectrophotometry, transmission electron mic…

Biocompatible hydrogels based on hyaluronic acid cross-linked with a polyaspartamide derivative as delivery systems for epithelial limbal cells.

2011

The aim of this work was to evaluate the potential use of hydrogels based on hyaluronic acid (HA) chemically cross-linked with α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-D,L-aspartamide (PHEA-EDA) as substitutes for the amniotic membrane able to release limbal cells for corneal regeneration. Hydrogels, shaped as films, with three different molar ratios (X) between PHEA-EDA and HA (X = 0.5, 1.0 and 1.5) have been investigated. First, it has been evaluated their swelling ability, hydrolytic resistance in simulated physiological fluid and cell compatibility by using human dermal fibroblasts chosen as a model cell line. Then adhesion studies in comparison with collagen gel, have been pe…

Disclosing the emissive surface traps in green-emitting carbon nanodots

2021

Abstract The bright photoluminescence of surface-functionalized carbon nanoparticles, known as carbon nanodots (CDs), has been studied for more than a decade because of its fundamental photo-physical interest and strong technological potential. However, the essential nature of the electronic states involved in their typical light emission remains very elusive. Here, we provide conclusive evidence that surface carboxylic moieties are the key to CD fluorescence. The synergy of nanosecond and femtosecond optical studies, cryogenic fluorescence, computational investigations and chemical engineering of a strategically chosen model CD system, allows to demonstrate that their visible-light transit…

In-situ forming gel-like depot of a polyaspartamide-polylactide copolymer for once a week administration of Sulpiride

2015

Abstract Objectives An in-situ forming gel-like depot, prepared by using an appropriate polyaspartamide-polylactide graft copolymer, has been employed to release in a sustained way sulpiride. Methods α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide-g-polylactic acid (PHEA-g-PLA) has been used as a polymer component. Its physicochemical properties make possible to dissolve it in N-methyl-2-pyrrolidone, with the obtainment of a solution able to form a gel-like depot once injected into a physiological medium. Cell compatibility of PHEA-g-PLA depot has been investigated, using murine dermal fibroblasts as cell model. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazo…

Cationic polyaspartamide-based nanocomplexes mediate siRNA entry and down-regulation of the pro-inflammatory mediator high mobility group box 1 in ai…

2015

Abstract High-mobility group box 1 (HMGB1) is a nonhistone protein secreted by airway epithelial cells in hyperinflammatory diseases such as asthma. In order to down-regulate HMGB1 expression in airway epithelial cells, siRNA directed against HMGB1 was delivered through nanocomplexes based on a cationic copolymer of poly(N-2-hydroxyethyl)- d,l -aspartamide (PHEA) by using H441 cells. Two copolymers were used in these experiments bearing respectively spermine side chains (PHEA-Spm) and both spermine and PEG2000 chains (PHEA-PEG-Spm). PHEA-Spm and PHEA-PEG-Spm derivatives complexed dsDNA oligonucleotides with a w/w ratio of 1 and higher as shown by a gel retardation assay. PHEA-Spm and PHEA-P…

Development of a simple, biocompatible and cost-effective Inulin-Diethylenetriamine based siRNA delivery system

2015

Small interfering RNAs (siRNAs) have the potential to be of therapeutic value for many human diseases. So far, however, a serious obstacle to their therapeutic use is represented by the absence of appropriate delivery systems able to protect them from degradation and to allow an efficient cellular uptake. In this work we developed a siRNA delivery system based on inulin (Inu), an abundant and natural polysaccharide. Inu was functionalized via the conjugation with diethylenetriamine (DETA) residues to form the complex Inu-DETA. We studied the size, surface charge and the shape of the Inu-DETA/siRNA complexes; additionally, the cytotoxicity, the silencing efficacy and the cell uptake-mechanis…

Composite nanoparticles based on hyaluronic acid chemically cross-linked with alpha,beta-polyaspartylhydrazide.

2007

In this paper, new composite nanoparticles based on hyaluronic acid (HA) chemically cross-linked with alpha,beta polyaspartylhydrazide (PAHy) were prepared by the use of a reversed-phase microemulsion technique. HA-PAHy nanoparticles were characterized by FT-IR spectroscopy, confirming the occurrence of the chemical cross-linking, dimensional analysis, and transmission electron micrography, showing a sub-micrometer size and spherical shape. Zeta potential measurements demonstrated the presence of HA on the nanoparticle surface. A remarkable affinity of the obtained nanoparticles toward aqueous media that simulate some biological fluids was found. Stability studies showed the absence of chem…

Gold nanostar–polymer hybrids for siRNA delivery: Polymer design towards colloidal stability and in vitro studies on breast cancer cells

2017

To overcome the low bioavailability of siRNA (small interfering RNA) and to improve their transfection efficiency, the use of non-viral delivery carriers is today a feasible approach to transform the discovery of these incredibly potent and versatile drugs into clinical practice. Polymer-modified gold nanoconstructs (AuNCs) are currently viewed as efficient and safe intracellular delivery carriers for siRNA, as they have the possibility to conjugate the ability to stably entrap and deliver siRNAs inside cells with the advantages of gold nanoparticles, which can act as theranostic agents and radiotherapy enhancers through laser-induced hyperthermia. In this study, AuNCs were prepared by coat…

Inhalable Formulation Based on Lipid–Polymer Hybrid Nanoparticles for the Macrophage Targeted Delivery of Roflumilast

2022

Here, novel lipid-polymer hybrid nanoparticles (LPHNPs), targeted to lung macrophages, were realized as potential carriers for Roflumilast administration in the management of chronic obstructive pulmonary disease (COPD). To achieve this, Roflumilast-loaded fluorescent polymeric nanoparticles, based on a polyaspartamide-polycaprolactone graft copolymer, and lipid vesicles, made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-distearoyl-sn-glycero-phosphoethanolamine-N-(polyethylene glycol)-mannose, were properly combined using a two-step method, successfully obtaining Roflumilast-loaded hybrid fluorescent nanoparticles (Man-LPHFNPs@Roflumilast). These exhibit colloidal size and a ne…

New biodegradable hydrogels based on a photo-cross-linkable polyaspartamide and poly(ethylene glycol) derivatives. Release studies of an anticancer d…

2001

The functionalization of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) with glycidyl methacrylate (GMA) gives rise to a water-soluble photosensitive copolymer PHEA-GMA (PHG). Aqueous solutions of PHG alone or in combination with various concentrations of poly(ethylene glycol) dimethacrylate or poly(ethylene glycol) diacrylate (PEGDA) have been exposed to a source of UV rays at 313 nm in order to obtain polymeric networks. All samples have been prepared both as water-swellable microparticles and as gel systems. Microparticles have been characterised by Fourier transform IR spectrophotometry, dimensional analysis and swelling measurements in aqueous media mimicking biological fluids. In vi…

A new hyaluronic acid pH sensitive derivative obtained by ATRP for potential oral administration of proteins

2013

Atom transfer radical polymerization (ATRP) has been successfully employed to obtain a new derivative of hyaluronic acid (HA) able to change its solubility as a function of external pH and then to be potentially useful for intestinal release of bioactive molecules, included enzymes and proteins. In particular, a macroinitiator has been prepared by linking 2-bromo-2-methypropionic acid (BMP) to the amino groups of ethylenediamino derivative of tetrabutyl ammonium salt of HA (HA-TBA-EDA). This macroinititor, named HA-TBA-EDA-BMP has been used for the ATRP of sodium methacrylate (MANa) using a complex of Cu(I) and 2,2'-bipyridyl (Byp) as a catalyst. The resulting copolymer, named HA-EDA-BMP-MA…

Effect of alkyl derivatization of gellan gum during the fabrication of electrospun membranes

2021

Electrospun nanofibers based on polysaccharides represent a consolidated approach in Tissue Engineering and Regenerative Medicine (TERM) and nanomedicine as a drug delivery system (DDS). In this work, two chemical derivatives of a low molecular weight gellan gum (96.7 kDa) with aliphatic pendant tails were processed by electrospinning technique into non-woven nanofibrous mats. In order to generate spinnable blends, it was necessary to associate poly vinyl alcohol (PVA). The relationships between the physicochemical properties and the processability via electrospinning technique of gellan gum alkyl derivatives (GG-C8 and GG-C12 having a degree of alkyl chain derivatization of 17 mol % and 1…

Combining inulin multifunctional polycation and magnetic nanoparticles: Redox-responsive siRNA-loaded systems for magnetofection

2019

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are recognized as one of the most promising agents for theranostic applications. Among methods designed for siRNA delivery, magnetofection, that is, nucleic acid cell uptake under the influence of a magnetic field acting on magnetic nucleic acid vectors, is emerging as a unique approach to combining advantages such as strong improvement of the kinetics of the delivery process and the possibility of localizing nucleic acid delivery to an area where the magnetic field is applied. This paper reports on the preparation of siRNA loaded magnetoplexes&mdash

Hybrid Gold/Silica/Quantum-Dots supramolecular-nanostructures encapsulated in polymeric micelles as potential theranostic tool for targeted cancer th…

2018

Abstract Efficient theranostic tools are today more and more frequently represented by the nano-sized systems. In this paper, polymeric micelles were produced and exploited to encapsulate both an antitumor drug (Doxorubicin) and gold core–shell quantum dots nanoparticles (Au-SiO2/QDs). α,β-poly(N-hydroxyethyl)- dl -aspartamide (PHEA) was functionalized with lipoic acid (LA), polyethylenglycol (PEG), and folic acid (FA) pendant moieties to obtain a synthetic derivative (PHEA-LA-PEG-FA) able to self assemble in aqueous medium giving rise to the formation of polymeric micelles exposing on their surface both targeting groups (FA) and hydrophilic chains (PEG). The drug carrying ability of PHEA-L…

Amphiphilic derivatives of a polyaspartamide: their aggregation and solubilization ability

2006

Abstract The self-aggregation and solubilization capability of a series of amphiphilic copolymers obtained by derivatisation of polymeric chain of α,β-poly(N-2-hydroxyethyl)- dl -aspartamide (PHEA) with polyethylene glycols (PEG, being different molecular weight 2000 or 5000 Da, PEG2000 and PEG5000, respectively) and/or hexadecylamine alkyl chain (C16), namely PHEA–PEG2000, PHEA–PEG5000, PHEA–C16, PHEA–PEG2000–C16 and PHEA–PEG5000–C16, have been evidenced by performing systematic tensiometric and spectrophotometric studies. All measurements have been performed at 25.0 °C over a wide copolymer concentration range. The tensiometric results have shown that, for all copolymers studied, the surf…

Interaction Between drug loaded Polyaspartamide-polylactide-polisorbate based micelles and cell membrane models: a calorimetric study

2011

Amphiphilic biodegradable copolymers, for their ability to self-assemble into micelle-like aggregates, with a suitable loading capacity, are of emerging interest for the delivery of water-insoluble drugs. α,β-Poly[(N-hydroxyethyl)-dl-aspartamide] (PHEA) is suitable to obtain amphiphilic graft copolymers. These copolymers can be obtained starting from PHEA-ethylenediamine (PHEA-EDA) which is functionalized with polysorbate 80 (PS₈₀, like targeting residues to the brain) and polylactide (PLA, like hydrophobic chains) in order to obtain polymeric micelles of PHEA-EDA-PS₈₀-PLA potentially useful to release drugs to the central nervous system. In this paper, the interaction and absorption of PHE…

PEG-benzofulvene copolymer hydrogels for antibody delivery.

2010

A new amphiphilic copolymer have been synthesized starting from the hydrosoluble polyaspartylhydrazide (PAHy) polymer, by grafting both hydrophilic PEG(2000) chains and hydrophobic palmitic acid (C(16)) moieties on polymer backbone, and the structure of obtained PAHy-PEG(2000)-C(16) copolymer have been characterized by 2D (1)H/(13)C NMR experiments. PAHy-PEG(2000)-C(16) copolymer showed the ability of self-assembling in aqueous media giving a core-shell structure and resulted potentially useful for encapsulating and dissolving hydrophobic drug. The formation of micellar core-shell structure has been investigated by 2D (1)H NMR NOESY experiments. The presence of cross-peaks for protons of C(…

Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells

2007

Introduction. The reaction between !,"-poly(aspartylhydrazide) (PAHy), a water soluble synthetic polymer and 3-(carboxypropyl)trimethyl-ammonium chloride (CPTACl) produced copolymers bearing permanent positive charges (PAHy–CPTA) with molecular weight of 10 kDa and PAHy–CPTA copolymers differing in positive charge amount (18–58%) were chosen for biological investigations. Materials and methods. Biophysical properties of DNA/PAHy–CPTA polyplexes were evaluated in terms of DNA condensation, zeta potential and size distribution. Cytotoxicity studies on Neuro2A murine neuroblastoma cells evidenced absence of toxicity of these copolymers up to 300 2g/ml unlike linear polyethylenimine (LPEI) that…

INULIN BASED HYDROGEL FOR ORAL DELIVERY OF FLUTAMIDE: PREPARATION, CHARACTERIZATION AND IN VIVO RELEASE STUDIES

2012

The ability of a hydrogel obtained by crosslinking INUDV and PEGBa to facilitate sustained release of flutamide is examined. The hydrogel is prepared in pH = 7.4 PBS and no toxic solvents or catalysts are used. It is recovered in microparticulate form and its size distribution is determined. Mucoadhesive properties are evaluated in vitro by reproducing gastrointestinal conditions. Flutamide is loaded into the hydrogel using a post-fabrication encapsulation procedure that allows a drug loading comparable to that of market tablets. Drug-loaded microparticles are orally administered to cross-bred dogs and the in vivo study demonstrates their ability to prolong the half-life of the principal ac…

Biocompatible polymeric micelles with polysorbate 80 for use in brain targeting.

2008

In this paper, the synthesis and characterization of novel amphiphilic graft copolymers based on an alpha,beta-poly(N-2-hydroxyethyl)-D, L-aspartamide (PHEA) backbone and D, L-polylactic acid (PLA) hydrophobic side chains are reported. These copolymers were obtained starting from PHEA-ethylenediamine (PHEA-EDA), which was functionalized with polysorbate 80 (PS(80)) and/or PLA in order to obtain the PHEA-EDA-PS(80)-PLA and PHEA-EDA-PLA samples, respectively. The degrees of derivatization, DD(PS80) and DD(PLA), of PHEA-EDA-PS80-PLA, calculated by (1)H-NMR, resulted in being 1.2 +/- 0.03 mol% and 0.54 +/- 0.05 mol%, respectively, while that of PHEA-EDA-PLA was found to be 0.60 +/- 0.05 mol%. S…

Uptake of silica covered Quantum Dots into living cells: Long term vitality and morphology study on hyaluronic acid biomaterials

2015

Quantum Dots (QDs) are promising very bright and stable fluorescent probes for optical studies in the biological field but water solubility and possible metal bio-contamination need to be addressed. In this work, a simple silica-QD hybrid system is prepared and the uptake in bovine chondrocytes living cells without any functionalization of the external protective silica shield is demonstrated. Moreover, long term treated cells vitality (up to 14 days) and the transfer of silica-QDs to the next cell generations are here reported. Confocal fluorescence microscopy was also used to determine the morphology of the so labelled cells and the relative silica-QDs distribution. Finally, we employ sil…

Carbon Nanodots as Functional Excipient to Develop Highly Stable and Smart PLGA Nanoparticles Useful in Cancer Theranostics

2020

Theranostic systems have attracted considerable attention for their multifunctional approach to cancer. Among these, carbon nanodots (CDs) emerged as luminescent nanomaterials due to their exceptional chemical properties, synthetic ease, biocompatibility, and for their photothermal and fluorescent properties useful in cancer photothermal therapy. However, premature renal excretion due to the small size of these particles limits their biomedical application. To overcome these limitations, here, hybrid poly(lactic-co-glycolic acid) (PLGA-CDs) nanoparticles with suitable size distribution and stability have been developed. CDs were decisive in the preparation of polymeric nanoparticles, not on…

Swellable microparticles containing Suprofen: evaluation of in vitro release and photochemical behaviour

1998

Suprofen, an anti-inflammatory drug was incorporated in polymer networks based on biocompatible macromolecules, such as alpha,beta-polyasparthydrazide (PAHy) and alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) crosslinked by glutaraldehyde or gamma-rays, respectively. Swelling tests carried out in aqueous media showed that pH value affects the swelling degree of the prepared hydrogels. In vitro release tests were performed in simulated gastrointestinal fluids (pH 1/6.8) using the pH variation method and in phosphate-buffered saline, pH 7.4. Experimental data indicated that Suprofen was released in a sustained way both from PAHy and PHEA microparticles. Further, incorporation of Suprof…

Mucoadhesive Solid Lipid Microparticles (SLM) for sustained release of corticosteroids to the lungs

2016

Pulmonary delivery is the preferred route of drug administration in the treatment of many respiratory disease, such as asthma and chronic obstructive pulmonary disease (COPD). Over the years, several kinds of carriers have been studied for sustained release of corticosteroids and bronchodilators to the lungs. Solid Lipid Microparticles (SLM) due to their biocompatibility and size (3-5 µm) can reach the bronchial epithelium directly, circumvent first pass metabolism and avoid systemic toxicity [1,2]. In this work we describe the preparation and the characterization of two different systems subjected to chitosan and alginate coating for sustained release of fluticasone propionate (FP) into th…

Synthesis and biopharmaceutical characterisation of new poly(hydroxyethylaspartamide) copolymers as drug carriers.

2001

Abstract Four new poly(hydroxyethylaspartamide)-based copolymers bearing (a) poly(ethylene glycol) 2000, (b) poly(ethylene glycol) 5000, (c) poly(ethylene glycol) 2000 and hexadecylalkyl, (d) poly(ethylene glycol) 5000 and hexadecylalkyle, as pendant groups were synthesised. The copolymers were obtained by partial aminolysis of polysuccinimide with poly(ethylene glycol) and hexadecylalkyl amino derivatives followed by reaction with ethanolamine. Naked polyhydroxyaspartamide was obtained by polysuccinimide reaction with ethanolamine. The nuclear magnetic resonance, infrared, light scattering and elemental analysis allowed for the extensive physico-chemical characterisation of the carriers. T…

Preparation and Characterization of Inulin Coated Gold Nanoparticles for Selective Delivery of Doxorubicin to Breast Cancer Cells

2016

A novel folate-targeted gold-based nanosystem for achieving selectivity towards folate receptor FR positive cells is proposed, by virtue of the fact that the FR is a molecularly targeted entity overexpressed in a wide spectrum of solid tumors. A new inulin-folate derivative INU-FA has been synthesized to act as coating agent for 40 nm gold nanoparticles. The obtained polymer-coated gold nanoparticles [email protected] were characterized in terms of hydrodynamic radius, shape, zeta potential, and aqueous stability and were loaded with doxorubicin [email protected]/Doxo. Its release capability was tested in different release media. The selectivity of [email protected]/Doxo system towards FRs-…

SUPRAMOLECULAR ASSOCIATION OF RECOMBINANT HUMAN GROWTH HORMONE WITH HYDROPHOBIZED POLYHYDROXYETHYLASPARTAMIDES

2008

Abstract The protein delivery properties of polymer supramolecular assemblies were investigated by using recombinant human growth hormone (rh-GH) and two polyhydroxyethylaspartamide (PHEA) derivatives: (a) PHEA-C 16 obtained by PHEA random grafting with hexadecylalkylamine; (b) PHEA-PEG 5000 -C 16 obtained by PHEA random co-grafting with hexadecylalkylamine and 5 kDa poly(ethylene glycol). The two polymers possessed similar self-assembling properties: critical micelle concentration (CMC) and particle size. The protein loading (protein/polymer, w/w, %) was 12.1 ± 1.3% and 8.5 ± 0.4% with PHEA-C 16 and PHEA-PEG 5000 -C 16 , respectively. The rh-GH/polymer association constant calculated by Sc…

Hydrogels for potential colon drug release by thiol-ene conjugate addition of a new inulin derivative.

2008

Inulin was chosen as a starting polymer for biocompatible, pH-sensitive and biodegradable hydrogels. Three INUDVSA-TT hydrogels were obtained by crosslinking inulin derivatives with trimethylolpropane tris(3-mercaptopropionate) under varying conditions. The resulting hydrogels were cell compatible, as demonstrated by MTS and trypan blue exclusion assays acting on Caco-2 cells, and were biodegraded by inulinase and esterase, thus suggesting their use as colonic drug delivery systems. 2-Methoxyestradiol, an anti-cancer drug, was soaked in INUDVSA-TT hydrogels and its in vitro release and apoptotic effect on Caco-2 cells were evaluated.

Near-Infrared Light Responsive Folate Targeted Gold Nanorods for Combined Photothermal-Chemotherapy of Osteosarcoma.

2017

Folate-targeted gold nanorods (GNRs) are proposed as selective theranostic agents for osteosarcoma treatment. An amphiphilic polysaccharide based graft-copolymer (INU-LA-PEG-FA) and an amino derivative of the α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide functionalized with folic acid (PHEA-EDA-FA), have been synthesized to act as coating agents for GNRs. The obtained polymer-coated GNRs were characterized in terms of size, shape, zeta potential, chemical composition, and aqueous stability. They protected the anticancer drug nutlin-3 and were able to deliver it efficiently in different physiological media. The ability of the proposed systems to selectively kill tumor cells was tested on U2OS…

Inulin-Ethylenediamine Coated SPIONs Magnetoplexes: A Promising Tool for Improving siRNA Delivery.

2015

An inulin based polycation (Inu-EDA) has been synthesized by the grafting of ethylenediamine molecules onto inulin backbone. The obtained inulin copolymer has been though to coat SPIONs (IC-SPIONs) and obtain stable magnetoplexes by complexation of IC-SPIONs with a model duplexed siRNA, for improving oligonucleotide transfection efficiency.The physical-chemical characteristics of IC-SPIONs and IC-SPIONs/siRNA magnetoplexes have been investigated by scanning and transmission electron microscopies, dynamic light scattering, FT-IR and qualitative surface elementary analysis. Cell compatibility and internalization in vitro of IC-SPIONs have been evaluated by MTS and fluorescence microscopy resp…

Ciprofloxacin releasing gellan gum/polydopamine based hydrogels with near infrared activated photothermal properties.

2021

Abstract In this work, with the aim to obtain a wound dressing hydrogel, an amine derivative of gellan gum was crosslinked in the presence of 4arm-polyethylenglycole-vinylsulfone. Through this easy and reproducible chemical procedure, a hydrogel with advanced elastic properties and hydrolytic resistance under physiological conditions was obtained. The incorporation of different quantities of polydopamine in the gelling solutions allows to obtain different hydrogels with marked photothermal properties when irradiated with a laser in the near infrared at 810 nm. The organic nanoparticles, reacting with the amino groups of the polysaccharide derivative, contribute to increase the storage modul…

Polymeric Nanocarriers for Magnetic Targeted Drug Delivery: Preparation, Characterization, and in Vitro and in Vivo Evaluation

2013

In this paper the preparation of magnetic nano- carriers (MNCs), containing superparamagnetic domains, is reported, useful as potential magnetically targeted drug delivery systems. The preparation of MNCs was performed by using the PHEA-IB-p(BMA) graft copolymer as coating material through the homogenization−solvent evaporation method. Magnetic and nonmagnetic nanocarriers containing flutamide (FLU-MNCs) were prepared. The prepared nanocarriers have been exhaustively characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and magnetic measurements. Biological evaluation was performed by in vitro cytotoxicity and cell uptake tests and in vivo biodistribution …

Hyaluronic Acid-g-Copolymers: Synthesis, Properties, and Applications

2013

The aim of this chapter is to review hyaluronic acid (HA) graft copolymers focusing in the description of chemical strategies employed for their synthesis, characterization procedures, and applications in biomedical and pharmaceutical field. Usually biocompatible synthetic polymers and peptides with therapeutic activity are grafted to HA to modify in appropriate way the physicochemical properties of the starting polysaccharide for a specific purpose and at the same time to exploit its biological role, biocompatibility, and targeting ability toward cells with receptors for HA. The use of such HA graft copolymers in the production of nanocarriers or hydrogels for modified drug release and sca…

Tamoxifen-loaded polymeric micelles: preparation, physico-chemical characterization and in vitro evaluation studies.

2004

Several samples of polymeric micelles, formed by amphiphilic derivatives of PHEA, obtained by grafting into polymeric backbone of PEGs and/or hexadecylamine groups (PHEA-PEG-C(16) and PHEA-C(16)) and containing different amount of Tamoxifen, were prepared. All Tamoxifen-loaded polymeric micelles showed to increase drug water solubility. TEM studies provided evidence of the formation of supramolecular core/shell architectures containing drug, in the nanoscopic range and with spherical shape. Samples with different amount of encapsulated Tamoxifen were subjected to in vitro cytotoxic studies in order to evaluate the effect of Tamoxifen micellization on cell growth inhibition. All samples of T…

BIOADHESIVE PROPERTIES OF A POLYAMINOACIDIC HYDROGEL: EVALUATION BY ATR FT-IR SPECTROSCOPY

2005

The bioadhesive properties of a novel chemical hydrogel based on a polymer of protein-like structure, have been investigated by using ATR FT-IR spectroscopy. In particular, the copolymer PHG obtained by partial derivatization of PHEA with GMA was chemically crosslinked by UV irradiation at 313 nm. Crosslinked PHG was treated with water to obtain a swelled sample, named PHG-UV gel, that was brought into contact with a phosphate buffer/citric acid solution at pH 7.0 in the absence or in the presence of mucin at various concentrations (0.01, 0.1 and 1 wt.-%). Preliminary dynamic swelling studies have evidenced the occurrence of an interaction between the PHG-UV gel and the glycoprotein. This r…

Fluoropolymer Based on a Polyaspartamide containing 1,2,4-Oxadiazole Units: A Potential Artificial Oxygen (O2) Carrier

2007

Abstract In this preliminary work we have prepared a fluorinated polymer capable of solubilizing an appreciable amount of O(2) and, at the same time, maintaining a higher water solubility than perfluoroalkanes investigated as injectable O(2) carriers. In particular, we describe the synthesis and characterization of a new macromolecular conjugate obtained by derivatization of alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) with 5-pentafluorophenyl-3-perfluoroheptyl-1,2,4-oxadiazole, called PHEA-F. This new water soluble fluoropolymer was prepared in high yield using a simple procedure. It was characterized by FT-IR and UV-vis spectrophotometry, (19)F-NMR and SEC measurements. O(2) so…

Polyanion–tobramycin nanocomplexes into functional microparticles for the treatment of Pseudomonas aeruginosa infections in cystic fibrosis

2016

Aim: Efficacy of antibiotics in cystic fibrosis (CF) is compromised by the poor penetration through mucus barrier. This work proposes a new ‘nano-into-micro’ approach, used to obtain a combinatorial effect: achieve a sustained delivery of tobramycin and overcome mucus barrier. Methods: Mannitol microparticles (MPs) were loaded with a tobramycin polymeric nanocomplex and characterized in presence of CF artificial mucus. Results & discussion: MPs are able to alter the rheological properties of CF artificial mucus, enhancing drug penetration into it and allowing a prolonged drug release. MPs resulted to be effective in Pseudomonas aeruginosa infections if compared with free tobramycin. Co…

An asymmetric electrospun membrane for the controlled release of ciprofloxacin and FGF-2: Evaluation of antimicrobial and chemoattractant properties.

2021

Here, an asymmetric double-layer membrane has been designed and fabricated by electrospinning as a tool for a potential wound healing application. A hydrophobic layer has been produced by using a polyurethane-polycaprolactone (PU-PCL) copolymer and loaded with the antibacterial ciprofloxacin whereas an ion responsive hydrophilic layer has been produced by using an octyl derivative of gellan gum (GG-C8) and polyvinyl alcohol (PVA) and loaded with the growth factor FGF-2. This study investigated how the properties of this asymmetric membrane loaded with actives, were influenced by the ionotropic crosslinking of the hydrophilic layer. In particular, the treatment in DPBS and the crosslinking i…

Mucus and Cell-Penetrating Nanoparticles Embedded in Nano-into-Micro Formulations for Pulmonary Delivery of Ivacaftor in Patients with Cystic Fibrosis

2017

Here, mucus-penetrating nanoparticles (NPs) for pulmonary administration of ivacaftor in patients with cystic fibrosis (CF) were produced with the dual aim of enhancing ivacaftor delivery to the airway epithelial cells, by rapid diffusion through the mucus barrier, and at the same time, promoting ivacaftor lung cellular uptake. Pegylated and Tat-decorated fluorescent nanoparticles (FNPs) were produced by nanoprecipitation, starting from two synthetic copolymers, and showed nanometric sizes (∼70 nm), a slightly negative ζ potential, and high cytocompatibility toward human bronchial epithelium cells. After having showed the significant presence of poly(ethylene glycol) chains and Tat protein …

Functionalization of a polyaspartamide with glycidyl methacrylate: A useful method to prepare hydrogels through gamma irradiation

1999

α-β-Poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) was derivatized with glycidyl methacrylate (GMA). Aqueous solutions of the obtained copolymer PHEA-GMA (PHG) were irradiated by gamma rays with a dose rate of 0.5 KGy/h and at zero °C in the presence or in the absence of N,N'-methylenebisacrylamide (BIS). New hydrogel systems were obtained and characterized by FT-IR analyses and swelling measurements in aqueous medium at different pH values.

Effect of pH on the transfer kinetics of an anti-inflammatory drug from polyaspartamide hydrogels to a lipid model membrane

1997

Abstract The release of a nonsteroidal anti-inflammatory drug (NSAID), 4-biphenylacetic acid (BPAA), from α,β-poly( N -hydroxyethyl)- dl -aspartamide (PHEA) hydrogels was tested at different pHs (4 and 7.4) by measuring the drug transfer from loaded hydrogel to dimyristoylphosphatidylcholine (DMPC) liposomes (multilamellar vesicles, MLV), chosen as a biomembrane model. This drug transfer was compared with the transfer from powdered drug and with drug classical. The perturbing effect of pure BPAA on the thermotropic behaviour of DMPC liposomes, in terms of transition temperature shift (Δ T m ) and enthalpy changes (Δ H ), was analysed at different pHs (4 and 7.4) by differential scanning cal…

Amphiphilic inulin graft co-polymers as self assembling micelles for doxorubicin delivery

2020

This paper reports the synthesis and characterization of a new amphiphilic inulin graft copolymer able to self-assemble in water into a micelle type structure and to deliver the anticancer model drug doxorubicin. For this aim, inulin was chemically modified in the side chain with primary amine groups (INU-EDA) and these were used as reactive moieties for the conjugation of poly ethylene glycol 2000 and succinyl-ceramide. The CMC of obtained amphiphilic inulin derivatives (INU-ceramide and INU-ceramide-PEG2000) was measured by means of fluorescence analysis using pyrene as the fluorescent probe. The obtained micelles were characterized by DLS and AFM analysis and the ability to release the l…

CONTROLLED RELEASE OF IgG BY NOVEL UV INDUCED POLYSACCHARIDE/POLY(AMINO ACID)HYDROGELS

2009

The development of new protein and peptide drugs needs new delivery systems able to entrap such drugs in safe conditions without affecting their structure and biological activity. In this context, the present work reports a new approach to load IgG, used as a model of therapeutic proteins such as anti-TNF-alpha monoclonal antibodies, into a polymeric system able to release the entrapped IgG in a controlled manner. In particular, new polysaccharide/poly(amino acid) UV induced hydrogels are proposed as colon delivery systems for human IgG. The poly(amino acid), alpha,beta-poly[N-(2-hydroxyethyl)-D,L-aspartamide], has been functionalized with methacrylic anhydride, while the polysaccharide, in…

Hyaluronan Graft Copolymers Bearing Fatty-Acid Residues as Self-Assembling Nanoparticles for Olanzapine Delivery

2019

In order to evaluate the potential of a technology platform based on hyaluronan copolymers grafted with propargylated ferulate fluorophores (HA-FA-Pg) in the development of drug delivery systems, the propargyl groups of HA-FA-Pg derivatives were employed with oleic acid (OA) or stearic acid (SA) residues across a biocompatible hexa(ethylene glycol) (HEG) spacer. The designed materials (i.e., HA-FA-HEG-OA or HA-FA-HEG-SA) showed clear-cut aggregation features in an aqueous environment, as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), generating nanoaggregate systems. In fact, HA-FA-HEG-OA and HA-FA-HEG-SA derivatives showed the property to create sel…

Synthesis of polymeric derivatives of isoniazid: characterization and in vitro release from a water-soluble adduct with polysuccinimide.

1989

Coupling of isoniazid with polysuccinimide afforded a water-insoluble polymeric pro-drug; by reaction with ethanolamine it was chemically transformed in a water-soluble adduct. The in vitro release of isoniazid from the drug-polymer adduct was studied by using an artificial stomach wall lipid membrane. The transfer rate constant from simulated gastric juice to simulated plasma was defined and compared with that of an equivalent dose of pure drug.

From Genesis to Revelation: The Role of Inflammatory Mediators in Chronic Respiratory Diseases and their Control by Nucleic Acid-based Drugs.

2015

Asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis, are among the most common chronic diseases and their prevalence is increasing. Each of these diseases is characterized by the secretion of cytokines and pro-inflammatory molecules which are thought to play a critical role in their pathogenesis. Moreover, immune cells, particularly neutrophils, macrophages and dendritic cells as well structural cells such as epithelial and airway smooth muscle cells are also involved in the pathogenic cycle of these diseases. There is a pressing need for the development of new therapies for these pulmonary diseases, particularly as no existing treatment has bee…

Biotin-Containing Reduced Graphene Oxide-Based Nanosystem as a Multieffect Anticancer Agent: Combining Hyperthermia with Targeted Chemotherapy

2015

Among the relevant properties of graphene derivatives, their ability of acting as an energy-converting device so as to produce heat (i.e., thermoablation and hyperthermia) was more recently taken into account for the treatment of solid tumors. In this pioneering study, for the first time, the in vitro RGO-induced hyperthermia was assessed and combined with the stimuli-sensitive anticancer effect of a biotinylated inulin-doxorubicin conjugate (CJ-PEGBT), hence, getting to a nanosystem endowed with synergic anticancer effects and high specificity. CJ-PEGBT was synthesized by linking pentynoic acid and citraconic acid to inulin. The citraconylamide pendants, used as pH reversible spacer, were …

NEW SELF-ASSEMBLING POLYASPARTYLHYDRAZIDE COPOLYMER MICELLES FOR ANTICANCER DRUG DELIVERY.

2010

A new amphiphilic copolymer have been synthesized starting from the hydrosoluble polyaspartylhydrazide (PAHy) polymer, by grafting both hydrophilic PEG(2000) chains and hydrophobic palmitic acid (C(16)) moieties on polymer backbone, and the structure of obtained PAHy-PEG(2000)-C(16) copolymer have been characterized by 2D (1)H/(13)C NMR experiments. PAHy-PEG(2000)-C(16) copolymer showed the ability of self-assembling in aqueous media giving a core-shell structure and resulted potentially useful for encapsulating and dissolving hydrophobic drug. The formation of micellar core-shell structure has been investigated by 2D (1)H NMR NOESY experiments. The presence of cross-peaks for protons of C(…

Hyaluronic acid based microparticles for applications in regenerative medicine

2018

Blend scaffolds with polyaspartamide/polyester structure fabricated via TIPS and their RGDC functionalization to promote osteoblast adhesion and prol…

2019

Target of this work was to prepare a RGDC functionalized hybrid biomaterial via TIPS technique to achieve a more efficient control of osteoblast adhesion and diffusion on the three-dimensional (3D) scaffolds. Starting from a crystalline poly(l-lactic acid) (PLLA) and an amorphous alpha,beta-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-d,l-aspartamide-graft-polylactic acid (PHEA-EDA-g-PLA) copolymer, blend scaffolds were characterized by an appropriate porosity and pore interconnection. The PHEA-EDA-PLA interpenetration with PLLA improved hydrolytic susceptibility of hybrid scaffolds. The presence of free amino groups on scaffolds allowed to tether the cyclic RGD peptide (RGDC) via Michael…

Addition reactions of azoesters with 2-thioquinazolinones

1981

Reaction between diethyl azodicarboxylate (I) and 1,2,3,4-tetrahydro-2-thioquinazolin-4-one (II), as a cyclic model of thiourea, both in alcoholic medium and in inert solvents has been investigated. By carrying out the reaction in an inert solvent, it was possible to isolate an intermediate. Evidence is presented that the intermediate, in turn, was converted into the final products. Structures were unequivocally assigned by mass spectrometry.

Perfluorocarbon functionalized hyaluronic acid derivatives as oxygenating systems for cell culture

2014

A set of new hyaluronic acid (HA) derivatives was obtained by binding fluorinated oxadiazole (OXA) moieties to an amino derivative of the polysaccharide (HA-EDA). The obtained HA-EDA-OXA biomaterials are potentially able to improve oxygenation into a scaffold for tissue engineering purposes. The oxygen solubility in aqueous dispersions of the obtained derivatives showed that polymers were able to improve oxygen uptake and maintenance in the medium. The HA-EDA-OXA was employed to form a hydrogel in situ by reaction with a vinyl sulphone derivative of inulin, under physiological conditions. The influence of the presence of OXA moieties on the mechanical properties of the obtained hydrogels as…

Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy.

2021

Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA graft copolymer were synthesized by chemical functionalisation with epidermal growth factor (EGF) or polyethylenglycol (PEG), named INU-IMI-DETA-EGF and INU-IMI-DETA-PEG, respectively, in order to improve the performance of already described “inulin complex nanoaggregates” (ICONs). The latter were thus prepared by appropriately mixing the two copolymers, by varying each component from 0 to 100 wt%…

Hyaluronic acid and alpha-elastin based hydrogel for three dimensional culture of vascular endothelial cells

2018

Abstract The aim of this work was to demonstrate that employing a copolymer of hyaluronic acid and α-elastin (HA-EDA-g-α-elastin) is possible to produce a scaffold able to support the adhesion and growth of human vascular endothelial cells (HUVEC) thanks to its ability to incorporate and control the diffusion of vascular endothelial growth factor (VEGF). HA-EDA-g-α-elastin was crosslinked with low molecular weight hyaluronic acid (HALMW) to obtain a hydrogel that gives rise to the formation of three dimensional sponge after the freeze drying process. The physicochemical features the obtained material along with its ability to act as a support for the three dimensional culture of endothelial…

Dexamethasone dipropionate loaded nanoparticles of α-elastin-g-PLGA for potential treatment of restenosis.

2013

A graft copolymer of α-elastin with poly(lactic-co-glycolic) acid (PLGA) has been synthesized and successfully employed to produce nanoparticles. Exploiting the known biological activity of α-elastin to promote the maintenance of smooth muscle cells (SMCs) contractile phenotype and the antiproliferative effect of glucocorticoids, the aim of this research was to produce drug-loaded nanoparticles suitable for potential treatment of restenosis. In particular, nanoparticles of α-elastin-g-PLGA with a mean size of 200 nm have been produced and loaded with dexamethasone dipropionate (10% w/w), chosen as a model drug that inhibits proliferation of vascular SMCs. These nanoparticles are able to pro…

Photocycle of Excitons in Nitrogen-Rich Carbon Nanodots: Implications for Photocatalysis and Photovoltaics

2020

Nitrogen-rich carbon nanodots have emerged as promising nanomaterials for a wide range of applications where a highly emissive and photoactive material with low toxicity and cost-effectiveness is required. One of their hallmarks is indeed a bright, tunable fluorescence of excitonic nature. Disentangling the origin of their optical absorption and fluorescence properties and uncovering relaxation channels and interactions with solvents are some of the most debated issues in the field. Uncovering these aspects is essential for targeted applications, especially in the fields of photocatalysis but also photovoltaics and optoelectronics. Here, we present dedicated transient absorption measurement…

Hyaluronic acid and beta cyclodextrins films for the release of corneal epithelial cells and dexamethasone

2016

In this work we prepared hydrogels based on hyaluronic acid and β-cyclodextrins to sustain the release of both corneal epithelial cells and dexamethasone. This steroid is administered as eye drops several times per day to reduce the risk of rejection in the post operative period after the cornea transplantation and cell release techniques. Hydrogels were produced by crosslinking an amino derivative of hyaluronic acid, with the divinyl sulfone derivative of β-cyclodextrins, this last employed as a crosslinker and solubilizing agent. Drug release studies revealed that dexamethasone containing samples are able to extend the release of this drug for at least five days. Biological studies, condu…

Disentangling size effects and spectral inhomogeneity in carbon nanodots by ultrafast dynamical hole-burning.

2018

Carbon nanodots (CDs) are a novel family of nanomaterials exhibiting unique optical properties. In particular, their bright and tunable fluorescence redefines the paradigm of carbon as a "black" material and is considered very appealing for many applications. While the field keeps growing, understanding CDs fundamental properties and relating them to their variable structures becomes more and more critical. Two crucial problems concern the effect of size on the electronic structure of CDs, and to what extent their optical properties are influenced by structural disorder. Furthermore, it remains largely unclear whether traditional concepts borrowed from the photo-physics of semiconductor qua…

Spray-Drying, Solvent-Casting and Freeze-Drying Techniques: a Comparative Study on their Suitability for the Enhancement of Drug Dissolution Rates.

2019

Purpose Solid dispersions (SDs) represent the most common formulation technique used to increase the dissolution rate of a drug. In this work, the three most common methods used to prepare SDs, namely spray-drying, solvent-casting and freezedrying, have been compared in order to investigate their effect on increasing drug dissolution rate. Methods Three formulation strategies were used to prepare a polymer mixture of polyvinyl-alcohol (PVA) and maltodextrin (MDX) as SDs loaded with the following three model drugs, all of which possess a poor solubility: Olanzapine, Dexamethasone, and Triamcinolone acetonide. The SDs obtained were analysed and compared in terms of drug particle size, drug-lo…

Photothermal nanofibrillar membrane based on hyaluronic acid and graphene oxide to treat Staphylococcus aureus and Pseudomonas aeruginosa infected wo…

2022

Here we reported the fabrication of an electrospun membrane based on a hyaluronic acid derivative (HA-EDA) to be used as a bandage for the potential treatment of chronic wounds. The membrane, loaded with graphene oxide (GO) and ciprofloxacin, showed photothermal properties and light-triggered drug release when irradiated with a near-infrared (NIR) laser beam. Free amino groups of HA-EDA derivative allowed autocrosslinking of the elec- trospun membrane; thus, a substantial enhancement in the hydrolytic resistance of the patch was obtained. In vitro antibacterial activity studies performed on Staphylococcus aureus and Pseudomonas aeruginosa revealed that such electrospun membranes, due to the…

Nanoaggregates Based on New Poly-Hydroxyethyl-Aspartamide Copolymers for Oral Insulin Absorption

2013

The aim of this work was to produce copolymers with an appropriate hydrophilic/hydrophobic balance able to form nanoaggregates with protein molecules and to be used as ideal materials in the field of oral peptide/protein delivery. New anionic polymers obtained by the conjugation of carboxy-bearing ligands, like succinic anhydride and/or cysteine, to hydrophobized α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) copolymers have been synthesized and characterized. Starting copolymer was synthesized by the partial derivatization of hydroxyl groups on the PHEA backbone with butylamine (C4) (obtaining the PHEA-C4 copolymer, bearing a butyl moiety). The consecutive reaction of PHEA-C4 with succin…

Evaluation of polyalkylcyanoacrylate nanoparticles as a potential drug carrier: preparation, morphological characterization and loading capacity.

1993

Some physicochemical behaviours were investigated of polyethyl- (PECA) and polyisobutylcyanoacrylate (PICA), which, in recent years, have been proposed as nanoparticle colloidal systems for drug carrying. We observed the influence of preparation conditions, such as pH value and surfactant concentration, on parameters such as particle size and polymer molecular weight. Lower operating pH values (0-2) resulted in smaller nanoparticles than those prepared at pH 5.5. The polymer molecular weight was also a function of pH: low molecular weight at low pH and vice-versa. The surfactant concentration positively influenced main particle size and polymer molecular weight. These trends were independen…

Nanostructured Lipid Carriers-Containing Anticancer Compounds: Preparation, Characterization, and Cytotoxicity Studies

2007

This article describes the development of nanostructured lipid carriers (NLC) as colloidal carriers for two antitumor compounds that possess a remarkable antineoplastic activity. But their limited stability and low solubility in water could give a very low parenteral bioavailability. Results revealed an enhancement of the cytotoxicity effect of drug-loaded NLC on human prostate cancer (PC-3) and human hepatocellular carcinoma (HuH-6, HuH-7) cell lines with respect to that of both free drugs. Results of characterization studies strongly support the potential application of these drugs-loaded NLC as prolonged delivery systems for lipophilic drugs by several administration routes, in particula…

Synthesis of Biocompatible and Biodegradable Polyamidoamines Microgels via a Simple and Reliable Statistical Approach.

2022

Polyamidoamines (PAAs) are biocompatible and biodegradable polymers with a huge potential as biomaterials for pharmaceutical applications. They are obtained by the step-wise aza-Michael polyaddition of bifunctional or multifunctional amines with bisacrylamides in water. To the best of our knowledge, no synthetic protocols leading to hyperbranched PAAs as well as PAA microgels have been published so far. To fill this gap, a statistical approach was established in this work to fine-tune the aza-Michael polyaddition stoichiometry when a multifunctional co-monomer (bf) is added to a mixture of bifunctional monomers with complementary functions (a2 + b2), possibly even in presence of a monofunct…

Reversibly stable thiopolyplexes for intracellular delivery of genes.

2006

Novel polyaspartamide non-viral carriers for gene therapy were synthesized by introducing, on the same polymer backbone, positively charged groups, for electrostatic interactions with DNA, and thiol groups for the formation of disulfide bridges between polymer chains. The introduction of thiols was aimed to have a vector with low redox potential sensitivity: disulfide crosslinking in fact, being stable in extracellular environment, allowed either to have stable complexes in plasma, that can protect DNA from metabolism, or to be reduced inside the cell, where the excess of glutathion in reduced form maintains a low redox potential. The consequent destabilization of the complex after disulfid…

New folate-functionalized biocompatible block copolymer micelles as potential anti-cancer drug delivery systems

2006

Abstract The main objective of this study was to synthesize novel folic acid-functionalized diblock copolymer micelles and evaluate their solubilization of two poorly water-soluble anti-tumor drugs, tamoxifen and paclitaxel, which suffer from low water solubility and/or poor hydrolytic stability. The diblock copolymer consisted of a permanently hydrophilic block comprising 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) residues and a pH-sensitive hydrophobic block comprising 2-(diisopropylamino)ethyl methacrylate (DPA) residues. Folic acid (FA) was conjugated to the end of the MPC block so that this group was located on the micelle periphery. Tamoxifen- and paclitaxel-loaded micelles were…

New hydrogel matrices containing an anti-inflammatory agent. Evaluation of in vitro release and photoprotective activity.

2002

In the present work. the preparation and characterization of hydrogels based on alpha,beta-polyaspartylhydrazide (PAHy) chemically crosslinked with ethyleneglycol diglycidylether (EGDGE) containing Tolmetin sodium salt, are reported. In particular, these samples have been prepared both as water swellable microparticles and as gels at two different crosslinking degrees. The incorporation of Tolmetin sodium salt in PAHy-EGDGE microparticles has been performed after the crosslinking reaction by a soaking procedure or during the formation of the network. The influence of drug loading procedure on Tolmetin release has been evaluated by performing in vitro release study in simulated gastrointesti…

Injectable in situ forming microgels of hyaluronic acid-g-polylactic acid for methylprednisolone release

2013

Abstract A hydrophobic derivative of hyaluronic acid (HA), obtained by grafting polylactic acid (PLA) to the polysaccharide, has been exploited to produce injectable in situ forming microgels. First of all, self assembling properties of HA-g-PLA copolymer have been evaluated by determining the critical aggregation concentration (CAC) value, then this copolymer has been dissolved in a mixture water/NMP 5:2 v/v with a concentration greater than CAC. When solutions at 1% or 2% w/v were injected into Dulbecco phosphate buffer solution (DPBS) pH 7.4, microgels promptly are formed. Their stability in DPBS pH 7.4 in the absence or in the presence of hyaluronidase and cell compatibility have been e…

Drug release from alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide-based microparticles.

2004

Abstract Spherical pH-sensitive microparticles have been prepared by reverse phase suspension polymerization technique. Starting polymer has been α , β -poly( N -2-hydroxyethyl)- dl -aspartamide (PHEA) partially derivatized with glycidylmethacrylate (GMA). PHEA-GMA copolymer (PHG) has been crosslinked in the presence of acrylic acid (AA) or methacrylic acid (MA) at various concentration. The obtained microparticles have been characterized by FT-IR spectrophotometry, particle size distribution analysis and scanning electron microscopy. In order to have information about water affinity of the prepared samples, swelling measurements have been carried out in aqueous media which simulate some bi…

Polybenzofulvene derivatives bearing dynamic binding sites as potential anticancer drug delivery systems.

2020

In order to obtain new advanced functional materials capable of recognizing drug molecules, the polybenzofulvene backbone of molecular brush poly-6-MOEG-9-TM-BF3k has been functionalized with a “synthetic dynamic receptor” composed of two 1-adamantylurea moieties linked together by means of a dipropyleneamino bridge as in Meijer's bis(adamantylurea) pincer (BAUP). This functional material, bearing synthetic receptors potentially capable of recognizing/loading and then delivering drug molecules, was used to prepare colloidal drug delivery systems (by means of soft interaction with BAUP) for delivering the model anti-cancer drug doxorubicin (DOXO). The resulting nanostructured drug delivery s…

Double-Network-Structured Graphene Oxide-Containing Nanogels as Photothermal Agents for the Treatment of Colorectal Cancer.

2017

Here, we reported the production of hyaluronic acid/polyaspartamide-based double-network nanogels for the potential treatment of colorectal carcinoma. Graphene oxide, thanks to the huge aromatic surface area, allows to easily load high amount of irinotecan (33.0% w/w) and confers to the system hyperthermic properties when irradiated with a near-infrared (NIR) laser beam. We demonstrate that the release of antitumor drug is influenced both by the pH of the external medium and the NIR irradiation process. In vitro biological studies, conducted on human colon cancer cells (HCT 116), revealed that nanogels are uptaken by the cancer cells and, in the presence of the antitumor drug, can produce a…

Design of New Polyaspartamide Copolymers for siRNA Delivery in Antiasthmatic Therapy

2020

Here, a novel protonable copolymer was realized for the production of polyplexes with a siRNA (inhibitor of STAT6 expression in asthma), with the aim of a pulmonary administration. The polycation was synthesized by derivatization of &alpha

Studies of macromolecular prodrugs of zidovudine.

2000

Abstract The current problems in controlling severe viral infections such as AIDS as well as the lack of effective and safe therapeutic measures for such diseases have caused interest in systems such as macromolecular prodrugs potentially able to solve heavier drawbacks of conventional antiviral therapy. This review focuses on various approaches proposed in the literature in this field. Neoglycoproteins and synthetic protein-like structure polymers have been mainly proposed. In the first group, the possibility of incorporating into the polymeric structures a determined amount of sugar molecules make them interesting candidates for targeting of infected blood cells. The conjugate of zidovudi…

Polyhydroxyethylaspartamide-based micelles for ocular drug delivery

2009

In this paper three copolymers of polyhydroxyethylaspartamide (PHEA), bearing in the side chains polyethylene glycol (PEG) and/or hexadecylamine (C(16)) (PHEA-PEG, PHEA-PEG-C(16) and PHEA-C(16) respectively) have been studied as potential colloidal drug carriers for ocular drug delivery. The physical characterization of all three PHEA derivatives, using the Langmuir trough (LT) and micellar affinity capillary electrophoresis (MACE) techniques allowed to assume that whereas alone PHEA backbone is an inert polymer with respect to the interactions with lipid membranes and drug complexation, when PHEA chains are grafted with long alkyl chains like C(16) or in combination C(16) chains and hydrop…

ChemInform Abstract: Reaction of 2-Acetyltetralone with Some Esters of Benzoic Acid.

1987

In order to investigate the pharmacological screening of a number of pyran-4-ones their synthesis by cyclization with sulphuric acid of the corresponding 1,3,5-triketones has been carried out with high yields. In the course of preparation of the latter the reaction of 2-acetyltetralone with some esters of benzoic acid derivatives has been studied and in particular, for a number of them, an interesting nucleophilic substitution of a chlorine atom with an alkoxy group on a benzenic nucleus has been evidenced.

Molecular characterization of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide derivatives as potential self-assembling copolymers forming polymeric micelles

2003

A family of graft copolymers derivatives obtained from α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) have been studied as potential self-assembling macromolecules forming stable polymeric micelles at low critical micellar concentration. These polymers are obtained grafting on PHEA poly(ethylene glycol) (PEG) (Mw 5000 g/mol) (PHEA–PEG), hexadecylamine (PHEA–C16) or both moieties (PHEA–PEG–C16). The PHEA derivatives were characterised by a multi-angle light scattering (MALS) photometer on line to a size exclusion chromatography system in obtaining the molar mass distribution of the polymers. In addition, to investigate the capacity to form micellar aggregates in aqueous medium the MALS pho…

SOLUBLE AND WATER-SWELLABLE POLYAMINOACIDIC CONSTRUCTS FOR DRUG DELIVERY

2004

Injectable in situ forming hydrogels based on natural and synthetic polymers for potential application in cartilage repair

2015

In this work we prepared two new hyaluronic acid (HA) based in situ forming hydrogels for the potential treatment of articular cartilage damages. In particular the amino derivative of HA (HA-EDA) and its graft copolymer with α-elastin (HA-EDA-g-α-elastin) were crosslinked, in mild physiological conditions via Michael-type addition, with α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) derivatized with divinylsulfone (DV). The swelling and degradation profile of the obtained hydrogels as well as the metabolic activity of incorporated bovine articular chondrocytes were investigated. Histological analysis and scanning electron microscopy (SEM) were performed to analyze the morphology of cells …

Carbon Nanodots for On Demand Chemophotothermal Therapy Combination to Elicit Necroptosis: Overcoming Apoptosis Resistance in Breast Cancer Cell Lines

2020

Background: Engineered luminescent carbon nanodots (CDs) are appealing nanomaterials for cancer image-guided photothermal therapy combining near infrared (NIR)&ndash

Effect of actively targeted copolymer coating on solid tumors eradication by gold nanorods-induced hyperthermia.

2020

Efforts in the field of anticancer therapy are increasingly focusing on the development of localized and selective treatments. Photothermal therapy (PTT) can lead to a spatially confined death of cancer cells, exploiting an increasing in temperature generated after UV-NIR irradiation of peculiar materials. Herein, a new actively targeted gold-based drug delivery system, named PHEA-LA-Fol-AuNRs/Iri, was explored for hyperthermia and chemotherapy colon cancer treatment. Gold nanorods were stabilized using a folate-derivative of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA-LA-PEG-FA) as coating agent and then loaded with the antineoplastic drug irinotecan (Iri). The efficacy of empty and i…

Inulin-based polymer coated SPIONs as potential drug delivery systems for targeted cancer therapy

2014

This paper deal with the synthesis and characterization of PEGylated squalene-grafted-inulin amphiphile capable of self-assembling and self-organizing into nanocarriers once placed in aqueous media. It was exploited as coating agent for obtaining doxorubicin loaded superparamagnetic iron oxide nanoparticles (SPIONs) endowed with stealth like behavior and excellent physicochemical stability. Inulin was firstly modified in the side chain with primary amine groups, followed in turn by conjugation with squalenoyl derivatives through common amidic coupling agents and PEGylation by imine linkage. Polymer coated SPIONs were so obtained by spontaneous self-assembling of inulin copolymer onto magnet…

Heparin functionalized polyaspartamide/polyester scaffold for potential blood vessel regeneration

2013

An interesting issue in tissue engineering is the development of a biodegradable vascular graft able to substitute a blood vessel and to allow its complete regeneration. Here, we report a new scaffold potentially useful as a synthetic vascular graft, produced through the electrospinning of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-D,L-aspartamide-graft-polylactic acid (PHEA-EDA-g-PLA) in the presence of polycaprolactone (PCL). The scaffold degradation profile has been evaluated as well as the possibility to bind heparin to electrospun fibers, being it a known anticoagulant molecule able to bind growth factors. In vitro cell compatibility has been investigated using human vascular e…

Photo-Cross-Linked Hydrogels with Polysaccharide−Poly(amino acid) Structure:  New Biomaterials for Pharmaceutical Applications

2006

The aim of this work has been the preparation and characterization of novel hydrogels with polysaccharide-poly(amino acid) structure having suitable physicochemical properties for pharmaceutical applications. In the first step, hyaluronic acid (HA) and alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) have been derivatized with methacrylic anhydride (AMA), thus obtaining HA-AMA and PHM derivatives, respectively. In the second step, aqueous solutions of both these derivatives have been irradiated at 313 nm to obtain chemical hydrogels. The hydrogel obtained by irradiating for 15 min an aqueous solution containing 4% w/v of HA-AMA and 4% w/v of PHM resulted in the highest yield. Its swe…

Salmeterol Xinafoate (SX) loaded into mucoadhesive solid lipid microparticles for COPD treatment

2019

Chronic obstructive pulmonary disease (COPD) is one of the main health problems worldwide. It is characterised by chronic inflammation in the lungs that leads to progressive, chronic, largely irreversible airflow obstruction. The use of long-acting β agonists remain today the frontline treatment for COPD with the aim of minimizing side effects and enhancing therapeutic usefulness. To this purpose, in this paper, mucoadhesive solid lipid microparticles (SLMs) containing a long-acting β-2 agonist, Salmeterol Xinafoate (SX) were prepared, characterised (size, z-potential, aerodynamic diameter, turbidimetric evaluations, drug loading and entrapping efficiency) and tested in a model of bronchial…

Polyaminoacid–doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy

2016

An amphiphilic copolymer carrying high-dose doxorubicin (21% on a weight basis), PHEA–EDA–P,C–Doxo, was prepared by coupling doxorubicin with a biocompatible polyaminoacid through a pH-sensitive spacer. Additional derivatization with 4-pentynoic acid endows it with self-assembling properties by means of π–π stacking. These micelles can be triggered to promptly release drug in lysosomes (∼40% in 12 h) through pH-dependent micelle hydrolysis after uptake. In vitro tests on co-cultures of cancer (MDA-MB 231) and normal (HB-2) breast cells proved that the conjugate was selectively internalized into the former rather than normal cells, exploiting the caveolae-dependent endocytosis pathway, expla…

SPIONs embedded in polyamino acid nanogels to synergistically treat tumor microenvironment and breast cancer cells.

2018

Abstract The extremely complex tumor microenvironment (TME) in humans is the major responsible for the therapeutic failure in cancer nanomedicine. A new concept of disease-driven nanomedicine, henceforth named “Theranomics”, which attempts to target cancer cells and TME on the whole, represents an attractive alternative. Herein, a nanomedicine able to co-deliver doxorubicin and a tumor suppressive proteolytic protein such as collagenase-2 was developed. We successfully obtained superparamagnetic nanogels (SPIONs/Doco@Col) via the intermolecular azide-alkyne Huisgen cycloaddition. We demonstrated that a local ECM degradation and remodeling in solid tumors by means of collagenase-2 could enha…

Correlating Rheological Properties of a Gellan Gum-Based Bioink: A Study of the Impact of Cell Density.

2022

Here, for the production of a bioink-based gellan gum, an amino derivative of this polysaccharide was mixed with a mono-functionalized aldehyde polyethyleneglycol in order to improve viscoelastic macroscopic properties and the potential processability by means of bioprinting techniques as confirmed by the printing tests. The dynamic Schiff base linkage between amino and aldehyde groups temporally modulates the rheological properties and allows a reduction of the applied pressure during extrusion followed by the recovery of gellan gum strength. Rheological properties, often related to printing resolution, were extensively investigated confirming pseudoplastic behavior and thermotropic and io…

α,β-poly(asparthylhydrazide)–glycidyltrimethylammonium chloride copolymers (PAHy–GTA): novel polymers with potential for DNA delivery

2001

Hydrophilic polycations form complexes when mixed with plasmids. Following functionalisation with glycidyltrimethylammonium chloride (GTA) alpha,beta-poly(asparthylhydrazide) (PAHy), a water-soluble synthetic macromolecule, becomes polycationic and potentially useful for systemic gene delivery. Initially the biocompatibility of PAHy and PAHy-GTA derivatives with different degrees of positive charge substitution were studied and it was shown that PAHy-GTA was neither haemolytic nor cytotoxicity up to 1 mg/ml. After intravenous injection (125)I-labelled PAHy-GTA derivative containing 46 mol% (PAHy-GTA(b)) of trimethylammonium groups did not accumulate in the liver (4.1+/-0.9% of the recovered…

Multifibrillar bundles of a self-assembling hyaluronic acid derivative obtained through a microfluidic technique for aortic smooth muscle cell orient…

2018

A hyaluronic acid derivative that is able to physically crosslink in a saline aqueous environment was employed for the production of fibers with a mean diameter of 50 μm using a microfluidic technique. The microfibers were collected in a tailored rotating collector and assembled to form multifibrillar bundles. The orientation of the microfibers on the collected bundles was evaluated by microCT analysis. The bundles were biofunctionalized by physical addition of fibronectin or chemical tethering of a cyRGDC peptide to achieve control of Aortic Smooth Muscle Cell (AoSMC) attachment, elongation and alignment. The mechanical performances of these bundles were evaluated by elongation tests, rela…

Galactosylated polyaspartamide copolymers for siRNA targeted delivery to hepatocellular carcinoma cells

2017

The limited efficacy of available treatments for hepatocellular carcinoma (HCC) requires the development of novel therapeutic approaches. We synthesized a novel cationic polymer based on α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) for drug delivery to HCC cells. The copolymer was synthesized by subsequent derivatization of PHEA with diethylene triamine (DETA) and with a polyethylene glycol (PEG) derivative bearing galactose (GAL) molecules, obtaining the cationic derivative PHEA-DETA-PEG-GAL. PHEA-DETA-PEG-GAL has suitable chemical-physical characteristics for a potential systemic use and can effectively deliver a siRNA (siE2F1) targeted against the transcription factor E2F1, a gen…

Self-organized environment-sensitive inulin–doxorubicin conjugate with a selective cytotoxic effect towards cancer cells

2015

An inulin-based random copolymer bearing high dose doxorubicin (18.45% on a weight basis), INU-EDA-P, C-DOXO, was prepared by coupling doxorubicin with inulin though a citraconylamide bridge used as a pH sensitive spacer. A further conjugation with pentynoic acid via an amidic bond led to the hydrophobization of the copolymer which allows the acquisition of a self-assembling ability at low concentration (0.33 mg mL(-1)) combining both Pi-Pi stacking and London interactions. Drug release studies were carried out at different pH demonstrating a remarkable pH dependency, where the maximum release rate was observed at pH mimicking cancer tissue and lysosomal environments. Besides, by measuring …

Lipid nanoparticles as delivery vehicles for the Parietaria judaica major allergen Par j 2

2011

Maria Luisa Bondì1,*, Giovanna Montana2,*, Emanuela Fabiola Craparo3, Roberto Di Gesù3, Gaetano Giammona3, Angela Bonura2, Paolo Colombo21Istituto per lo Studio dei Materiali Nanostrutturati, 2Istituto di Biomedicina ed Immunologia Molecolare, Consiglio Nazionale delle Ricerche, 3Laboratory of Biocompatible Polymers, Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari Stembio, Università di Palermo, Palermo, Italy *These authors contributed equally to this workAbstract: Parietaria pollen is one of the major causes of allergic reaction in southern Europe, affecting about 30% of all allergic patients in this area. Specific immunotherapy is the only…

Reactions of azoesters and dimethyl acetylenedicarboxylate with 3-methyl-1,2,4-triazole-5-thione

1991

The addition of dimethyl acetylenedicarboxylate to 3-methyl-1,2,4-triazole-5-thione (1), both in alcoholic medium and in inert solvents, has been investigated. When 1 was allowed to react with diethyl azodicarboxylate a disulfide 5 was obtained.

Peculiar mechanism of solubilization of a sparingly water soluble drug into polymeric micelles. Kinetic and equilibrium studies.

2012

Complementary kinetic and equilibrium studies on the solubilization process of the sparingly water soluble tamoxifen (TAM) drug in polymeric aqueous solutions have been performed by using the spectrophotometric method. In particular, the amphiphilic copolymers obtained by derivatization of polymeric chain of poly(N-2-hydroxyethyl)-dl-aspartamide, PHEA, with poly(ethylene glycol)s, PEG (2000 or 5000 Da), and/or hexadecylamine chain, C16, namely PHEA-PEG2000-C16, PHEA-PEG5000-C16, PHEA-C16, have been employed. Preliminary to the kinetic and equilibrium data quantitative treatment, the molar absorption coefficient of TAM in polymeric micelle aqueous solution has been determined. By these studi…

Galactosylated Polymer/Gold Nanorods Nanocomposites for Sustained and Pulsed Chemo-Photothermal Treatments of Hepatocarcinoma

2022

In this paper, we propose a rational design of a hybrid nanosystem capable of locally delivering a high amount of hydrophobic anticancer drugs (sorafenib or lenvatinib) and heat (hyperthermia) in a remote-controlled manner. We combined in a unique nanosystem the excellent NIR photothermal conversion of gold nanorods (AuNRs) with the ability of a specially designed galactosylated amphiphilic graft copolymer (PHEA-g-BIB-pButMA-g-PEG-GAL) able to recognize hepatic cells overexpressing the asialoglycoprotein receptor (ASGPR) on their membranes, thus giving rise to a smart composite nanosystem for the NIR-triggered chemo-phototherapy of hepatocarcinoma. In order to allow the internalization of A…

Self-assembling and auto-crosslinkable hyaluronic acid hydrogels with a fibrillar structure

2008

Abstract A hyaluronic acid derivative bearing pendant l -benzoyl-cysteine portions (with a derivatization degree equal to 10 mol.%) was synthesized by linking N,N′-dibenzoyl- l -cystine to the polysaccharide and then reducing its disulfide bridge to thiol groups. The formation of π–π stacking interactions between the benzoyl moieties was studied by fluorescence spectroscopy as a function of polymer concentration and oxidation time. The efficiency of oxidation of thiol groups to disulfide bridges occurring in phosphate buffer pH 7.4, was determined by colorimetric assays. The hydrogel formed by means of oxidative crosslinking has shown the presence of fibrillar aggregates as detected by ligh…

Microfibrillar polymeric ocular inserts for triamcinolone acetonide delivery.

2019

Abstract Despite eye drops generally represent the most convenient, simple and patient-friendly formulations to treat ocular diseases, they suffer from poor retention on the ocular surface and low drug bioavailability leading to the necessity of prolonged and continuous treatment over time. Therefore, ocular insert could represent an innovative way to benefit from ocular topical administration while minimizing all the relevant limitation related to this route of administration. Polymeric non-erodible mucoadhesive ocular inserts should be comfortable and should rapidly adhere on the ocular surface, remain in situ for prolonged period, assure a reproducible and controlled drug release as well…

Photocrosslinking of dextran and polyaspartamide derivatives: a combination suitable for colon-specific drug delivery.

2007

Abstract The aim of this study was to prepare and characterize novel hydrogels with polysaccharide–polyaminoacid structure, able to undergo an enzymatic hydrolysis in the colon and potentially useful for treating inflammatory bowel diseases (IBD). Starting materials were methacrylated dextran (DEX-MA) and methacrylated α,β-poly(N-2-hydroxyethyl)- dl -aspartamide (PHM). These polymers were photocrosslinked by exposure of their aqueous solutions at 313 nm without photoinitiators. Different samples, shaped as microparticles, were obtained as a function of polymer concentration and irradiation time. FT-IR analysis confirmed the occurrence of a co-crosslinking between DEX-MA and PHM in all exper…

Hydrophilic and hydrophobic copolymers of a polyasparthylhydrazide bearing positive charges as vector for gene therapy

2008

BACKGROUND: The design of polymeric vectors for gene delivery provided with specific properties is one of the most critical aspects for a successful gene therapy. These polymers should be biocompatible as well as able to carry efficiently DNA to target tissues and to transfect it into cells. RESULTS: The formation of complexes of poly[(α,β-asparthylhydrazide)–poly(ethylene glycol)] and poly[(α,β-asparthylhydrazide)–hexadecylamine] copolymers functionalised with glycidyltrimethylammonium chloride (PAHy–PEG-GTA and PAHy–C16-GTA, respectively) with DNA was studied. The effects of the introduction of hydrophilic (PEG) or hydrophobic (C16) moieties on the chains of PAHy–GTA copolymers, such as t…

Inulin-Based Polymeric Micelles Functionalized with Ocular Permeation Enhancers: Improvement of Dexamethasone Permeation/Penetration through Bovine C…

2021

Ophthalmic drug delivery is still a challenge due to the protective barriers of the eye. A common strategy to promote drug absorption is the use of ocular permeation enhancers, while an innovative approach is the use of polymeric micelles. In the present work, the two mentioned approaches were coupled by conjugating ocular permeation enhancers (PEG2000, carnitine, creatine, taurine) to an inulin-based co-polymer (INU-EDA-RA) in order to obtain self-assembling biopolymers with permeation enhancer properties for the hydrophobic drug dexamethasone (DEX). Inulin derivatives were properly synthetized, were found to expose about 2% mol/mol of enhancer molecules in the side chain, and resulted abl…

Hydrogels containing 5-Fluorouracil obtained by γ-irradiation. Synthesis, characterization and in vitro release studies

2001

The functionalization of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) with glycidyl methacrylate (GMA) gives rise to a water-soluble copolymer PHEA-GMA (PHG) containing double bonds and ester groups in the side chain. Aqueous solutions of PHG alone or in combination with N,N′ methylenbisacrylamide (BIS) have been exposed to a γ-ray source at different irradiation doses in order to obtain polymeric networks. All samples have been prepared both as water-swellable microparticles and as gel systems. Microparticles have been characterized by FT-IR spectrophotometry and swelling measurements in aqueous media mimicking biological fluids. The effect of irradiation dose and BIS presence on rheol…

SYNTHESIS, PHYSICO-CHEMICAL AND BIOLOGICAL CHARACTERIZATION OF A PACLITAXEL MACROMOLECULAR PRODRUG

2004

Paclitaxel was attached to poly(hydroxyethylaspartamide) via a succinic spacer arm by a two-step protocol: (1) synthesis of 2'-O-succinyl-paclitaxel; (2) synthesis of PHEA-2'-O-succinyl-paclitaxel. The 2'-O-succinyl-paclitaxel derivative and the macromolecular conjugate were characterized by UV, IR, NMR and mass spectrometry analysis. The reaction yields were over 95% and the purity of products over 98%. Paclitaxel release and degradation from 2'-O-succinyl-paclitaxel occurred at a faster rate at pH 5.5 than 7.4. After 30 h of incubation at pH 5.5 and 7.4 the released free paclitaxel was about 40 and 20%, respectively. In plasma both drug release and degradation were found to occur at a hig…

A hyaluronic acid/cyclodextrin based injectable hydrogel for local doxorubicin delivery to solid tumors

2020

Localized delivery of anticancer drugs is often the most useful therapeutic approach for the treatment of solid tumors. The use of injectable polymeric systems that maximize drug concentration in the proximal area of the tumor represents an extremely advantageous therapeutic strategy. Here, the development of an injectable in situ forming hydrogel was accomplished by exploiting the azo-type Michael reaction between an amine derivative of hyaluronic and vinylsulfone functionalized -cyclodextrins complexing doxorubicin. This injectable system can be easily prepared and administered with timelines compatible with normal operating room procedures, as demonstrated by rheological tests. In vitro…

A fluorescent molecular sensor for pH windows in traditional and polymeric biocompatible micelles: comicellization of anionic species to shift and re…

2011

A new approach is presented to obtain fluorescent sensors for pH windows that work in water and under biomimetic conditions. A single molecule that features all-covalently linked components is used, thus making it capable of working as a fluorescent sensor with an OFF/ON/OFF response to pH value. The components are a tertiary amine, a pyridine, and a fluorophore (pyrene). The forms with both protonated bases or both neutral bases quench the pyrene fluorescence, whereas the form with the neutral pyridine and protonated amine groups is fluorescent. The molecular sensor is also equipped with a long alkyl chain to make it highly hydrophobic in all its protonated and unprotonated forms, that is,…

SYNTHESIS, CHARACTERIZATION AND IN VITRO CYTOTOXICITY STUDIES OF A MACROMOLECULAR CONJUGATE OF PACLITAXEL BEARING OXYTOCIN AS TARGETING MOIETY.

2007

The present study describes the experimental synthetic procedure and the characterization of a new polyaspartamide macromolecular prodrug of paclitaxel, bearing oxytocin residues as targeting moieties. In vitro stability studies of bioconjugate, performed in media mimicking biological fluids (buffer solutions at pH 7.4 and 5.5) and in human plasma, evidenced the high stability of the targeting portion (oxytocin)-polymer linkage and the ability of this conjugate to release linked paclitaxel in a prolonged way in plasma. Moreover, preliminary in vitro antiproliferative studies, carried out on MCF-7 cells, that are oxytocin receptor positive cells, showed that the polymeric conjugate has the s…

Polymer-based systems for controlled release and targeting of drugs

2019

The current need to find new advanced approaches to carry biologically active substances (conventional organic drugs, peptides, proteins (such as antibodies), and nucleic acid-based drugs (NABDs such as siRNA and miRNA)) in the body fluids, to realize targeted therapies and even personalized ones, goes hand in hand with research on the performance of new materials to better realize appropriate drug vectors [...]

in vitro biological evaluation of folate-functionalized block copolymer micelles for selective anti-cancer drug delivery.

2008

The main objective of this study was to evaluate the ability of folic acid-functionalized diblock copolymer micelles to improve the delivery and uptake of two poorly water-soluble anti-tumor drugs, tamoxifen and paclitaxel, to cancer cells through folate receptor targeting. The diblock copolymer used in this study comprised a hydrophilic poly[2-(methacryloyloxy)ethyl phosphorylcholine] (MPC) block, carrying at the chain end the folate targeting moiety, and a pH-sensitive hydrophobic poly[2-(diisopropylamino)ethyl methacrylate] (DPA) block (FA-MPC-DPA). The drug-loading capacities of tamoxifen- and paclitaxel-loaded micelles were determined by high performance liquid chromatography and the m…

Solid Lipid Nanoparticles Containing Nimesulide: Preparation, Characterization and Cytotoxicity Studies

2009

The prospect of improved cancer therapy using Solid Lipid Nanoparticles (SLNs) as drug delivery system is promising. Sev- eral obstacles frequently encountered with anticancer compounds, such as poor drug solubility, are overcome by delivering them using SLN. Moreover, the intravenous administration of drugs into SLNs can potentially enhance drug blood circulation time and improve drug per- formance by inducing accumulation into tumours by enhanced permeability and retention (EPR) effect. This paper deals with the devel- opment of SLN containing nimesulide, a non-steroidal anti-inflammatory drug with antitumour effect and low solubility in water. Here, SLNs carrying nimesulide were prepared…

Polyhydroxyethylaspartamide-spermine copolymers: Efficient vectors for gene delivery

2008

Abstract Aim of this paper was that to prepare biocompatible, polyaspartamide based copolymers containing spermine or spermine/hydrophobic side chains able to condense nucleic acids and to transfect mammalian cells. Copolymers were prepared starting from α,β-poly-(N-2-hydroxyethyl)- d , l -aspartamide (PHEA) and exploiting the reactive hydroxyl groups in the polymeric side chains by subsequent activation reactions to obtain PHEA-Spermine (PHEA-Spm) and PHEA-Spermine-Butyramide (PHEA-Spm-C4). Molecular, physico-chemical and biological characterization of copolymers and interpolyelectrolyte complexes with plasmid DNA was performed. Experimental results evidenced that these copolymers are able…

Branched High Molecular Weight Glycopolypeptide With Broad-Spectrum Antimicrobial Activity for the Treatment of Biofilm Related Infections.

2017

There are few therapeutic options to simultaneously tackle Staphylococcus aureus and Pseudomonas aeruginosa, two of the most relevant nosocomial and antibiotic-resistant pathogens responsible for implant, catheters and wound severe infections. The design and synthesis of polymers with inherent antimicrobial activity have gained increasing attention as a safe strategy to treat multi-drug-resistant microbes. Here, we tested the activity of a new polymeric derivative with glycopolypeptide architecture (PAA-VC) bearing l-arginine, vancomycin, and colistin as side chains acting against multiple targets, which give rise to a broad spectrum antimicrobial activity favorably combining specific and n…

Enhanced adhesion and in situ photothermal ablation of cancer cells in surface-functionalized electrospun microfiber scaffold with graphene oxide

2017

The physicochemical characteristics of a biomaterial surface highly affect the interaction with living cells. Recently, much attention has been focused on the adhesion properties of functional biomaterials toward cancer cells, since is expected to control metastatic spread of a tumor, which is related to good probability containing the progression of disease burden. Here, we designed an implantable poly(caprolactone)-based electrospun microfiber scaffold, henceforth PCLMF-GO, to simultaneously capture and kill cancer cells by tuning physicochemical features of the hybrid surface through nitrogen plasma activation and hetero-phase graphene oxide (GO) covalent functionalization. The surface i…

Novel polyaminoacidic copolymers as nonviral gene vectors

2000

Human gene therapy is one of the most promising methods developed in recent years, providing great potential for the treatment of a variety of diseases. Complexes formed between DNA and cationic polymers are attracting increasing attention as novel synthetic vectors for the delivery of genes. We have synthesized polycations with quaternary ammonium groups in their side chains for self-assembly with calf thymus DNA. This paper describes the functionalization of α,β-polyasparthydrazide (PAHy), a synthetic macromolecule having many potential applications in the field of biomedical sciences, with glycidyltrimethylammonuim chloride (GTA) in order to introduce positive charges into their chains. …

Polyaspartamide-graft- Polymethacrylate Nanoparticles for Doxorubicin Delivery

2011

A new PHEA-IB-PMANa + copolymer has been synthesized and its pH-induced self-assembly has been investigated in an aqueous medium. PHEA-IB-PMANa + formed nanoparticles with diameters from 25 to 50 nm upon protonation of the carboxylic acid moieties dislocated along the grafted polymethacrylate sodium salt side chains. The physico-chemical characterization of the nanoparticles was performed using light scattering, zeta-potential measurements, SEM, and AFM. Doxorubicin-loaded nanoparticles were prepared and drug release profiles were evaluated under conditions mimicking physiological media. A biological characterization was carried out by testing the cytotoxicity on Caco-2 cells, and cellular …

Molecular characterization of α,β-poly[( N -hydroxyethyl)- dl –aspartamide] by light scattering and viscometry studies

2000

Abstract α,β-poly[(N-hydroxyethyl)- dl -aspartamide] (PHEA) is a new synthetic polymer which is of interest in biomedical applications. In this paper, the molecular characterization of PHEA by multi-angle laser light scattering and viscometry off-line and on-line to a size exclusion chromatography system is reported. These techniques furnish an exhaustive and consistent characterization of the PHEA polymer. The fractionation of the PHEA macromolecules was relatively simple. Using an aqueous mobile phase of medium ionic strength, the elution was substantially regular and the macromolecules were not aggregate. The molar mass M of four PHEA samples approximately ranges from 46 to 53 K g/mol, t…

Spray dried hyaluronic acid microparticles for adhesion controlled aggregation and potential stimulation of stem cells

2017

Spray-dried microparticles of a derivative of hyaluronic acid (HA) have been engineered to obtain a controlled aggregation with Human Mesenchymal Stem Cells (hMSCs) into 3D constructs. We demonstrated the utility of chemical functionalization of a native constituent of the extracellular matrix to improve processing performances and to control on stem cell adhesion and differentiation. Native hyaluronic acid (HA), cell adhesive peptides (RGD), transforming growth factor β3, dexamethasone are biological agents potentially suitable for chondrogenic stimulation of hMSCS. However unmodified HA suffers of drawbacks in terms of stability and versatility of processing. Functionalization strategies…

New hyaluronic acid based brush copolymers synthesized by atom transfer radical polymerization.

2013

Abstract In this work, an efficient method for the synthesis of hyaluronic acid based brush copolymers using atom transfer radical polymerization (ATRP) has been reported. At first, two different hyaluronic acid (HA) based macroinitiators have been prepared and then they have been used for the polymerization via ATRP of hydrophilic or hydrophobic molecules carrying vinyl portions. In particular, by linking 2-bromo-2-methylpropionic acid (BMP) to the primary hydroxyl groups of tetrabutyl ammonium salt of HA (HA–TBA) or to amino groups of the ethylenediamino derivative of HA–TBA (HA–TBA–EDA), two macroinitiators (HA–TBA–BMP and HA–TBA–EDA–BMP) have been obtained. Then they have been used for …

Inulin coated plasmonic gold nanoparticles as a tumor-selective tool for cancer therapy.

2015

Preferential uptake by cancer cells of PEG-inulin coated gold nanoparticles loaded with the drug doxorubicin.

Evaluation of mucoadhesive properties of α,β-poly(N-hydroxyethyl)-dl-aspartamide and α,β-poly(aspartylhydrazide) using ATR–FTIR spectroscopy

2002

Abstract The mucoadhesive properties of α,β poly( N -hydroxyethyl)- dl -aspartamide (PHEA) and α,β-polyaspartylhydrazide (PAHy) have been investigated using attenuated total reflection infrared (ATR–FTIR) spectroscopy. In particular, films based on these polymers have been contacted with a mucin solution at pH 7 and, the interfacial interaction and interpenetration between the glycoprotein and PHEA or PAHy have been studied by analysing the ATR–FTIR spectra. A diffusion model using a solution of Ficks' second law has been employed to determine the diffusion coefficient of water into polymeric films as a consequence of interdiffusion which occurs at the polymer film/mucin solution interface.

Polybutylene succinate artificial scaffold for peripheral nerve regeneration

2021

Regeneration and recovery of nerve tissues are a great challenge for medicine, and positively affect the quality of life of patients. The development of tissue engineering offers a new approach to the problem with the creation of multifunctional artificial scaffolds that act on various levels in the damaged tissue, providing physical and biochemical support for the growth of nerve cells. In this study, the effects of the use of a tubular scaffold made of polybutylene succinate (PBS), surgically positioned at the level of a sciatic nerve injured in rat, between the proximal stump and the distal one, was investigated. Scaffolds characterization was carried out by scanning electron microscopy …

Nano into Micro Formulations of Tobramycin for the Treatment of Pseudomonas aeruginosa Infections in Cystic Fibrosis.

2017

Here, nano into micro formulations (NiMs) of tobramycin for the treatment of Pseudomonas aeruginosa airway infections in cystic fibrosis (CF) are described. NiMs were produced by spray drying a solution containing polymers or sugars and a nanometric polyanion–tobramcyin complex (PTC), able to achieve a prolonged antibiotic release. NiMs properties were compared to TOBIPodhaler(Novartis), the only one commercially available dry powder inhalatory formulation based on porous microparticles. Produced NiMs showed adequate characteristics for pulmonary administration, as spherical shape, micrometric size, and high cytocompatibility toward human bronchial epithelial cells. Contrarily to TOBIPodhal…

Chemical hydrogels based on a hyaluronic acid-graft-α-elastin derivative as potential scaffolds for tissue engineering

2013

In this work hyaluronic acid (HA) functionalized with ethylenediamine (EDA) has been employed to graft α-elastin. In particular a HA-EDA derivative bearing 50 mol% of pendant amino groups has been successfully employed to produce the copolymer HA-EDA-g-α-elastin containing 32% w/w of protein. After grafting with α-elastin, remaining free amino groups reacted with ethylene glycol diglycidyl ether (EGDGE) for producing chemical hydrogels, proposed as scaffolds for tissue engineering. Swelling degree, resistance to chemical and enzymatic hydrolysis, as well as preliminary biological properties of HA-EDA-g-α-elastin/EGDGE scaffold have been evaluated and compared with a HA-EDA/EGDGE scaffold. T…

Nanometric ion pair complexes of tobramycin forming microparticles for the treatment of Pseudomonas aeruginosa infections in cystic fibrosis

2019

Abstract Sustained pulmonary delivery of tobramycin from microparticles composed of drug/polymer nanocomplexes offers several advantages against traditional delivery methods. Namely, in patients with cystic fibrosis, microparticle delivery can protect the tobramycin being delivered from strong mucoadhesive interactions, thus avoiding effects on its diffusion toward the infection site. Polymeric ion-pair complexes were obtained starting from two synthetic polyanions, through impregnation of their solid dissociated forms with tobramycin in aqueous solution. The structure of these polymeric systems was characterized, and their activities were examined against various biofilm-forming Pseudomona…

EMPLOYMENT OF CATIONIC SOLID-LIPID NANOPARTICLES AS RNA CARRIERS

2007

Gene transfer represents an important advance in the treatment of both genetic and acquired diseases. In this article, the suitability of cationically modified solid-lipid nanoparticles (SLN) as a nonviral vector for gene delivery was investigated, in order to obtain stable materials able to condense RNA. Cationic SLN were produced by microemulsion using Compritol ATO 888 as matrix lipid, Pluronic F68 as tenside, and dimethyldioctadecylammonium bromide (DDAB) as cationic lipid. The resulting particles were approximately 100 nm in size and showed a highly positive surface charge (+41 mV) in water. Size and shape were further characterized by scanning electron microscopy (SEM) measurements. M…

New Biodegradable Hydrogels Based on Inulin and α,β-Polyaspartylhydrazide Designed for Colonic Drug Delivery: In Vitro Release of Glutathione and Oxy…

2010

Succinic derivatives of inulin (INU-SA) with two different degrees of derivatization (20% and 30%, mol/mol) were cross-linked with α,β-polyaspartylhydrazide (PAHy) to obtain INUPAHy hydrogels. Cross-linking was performed using N-ethyl-N-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC) and N-hydroxysulfosuccinimide (NHSS) as coupling agents and by varying the reaction time (4 h, 8 h and 24 h). All samples prepared were characterized by FT-IR analysis and swelling measurements in different media. In vitro assays, performed in the presence of inulinase, demonstrated the degradability of the prepared hydrogels. Cell compatibility was evaluated using Caco-2 cells through both direct and …

Synthesis and characterization of water-swellable?,?-polyasparthydrazide derivatives

1995

α, β-polyasparthydrazide (PAHy) was crosslinked by glutaraldehyde to form water-swellable materials possessing a three-dimensional molecular network. Different crosslinking degrees were prepared varying glutaraldehyde/PAHy ratio and samples containing 5-fluorouracil were obtained by incorporating the drug into the polymer networks during the crosslinking reaction. All samples were characterized by swelling tests, thermal, x-ray and SEM analysis. Their microstructure was observed through scanning electron microscopy. Furthermore, for samples containing the anticancer drug,in vitro release studies were performed in pH 7.4 buffer solution.

Polyaspartamide based hydrogel with cell recruitment properties for the local administration of hydrophobic anticancer drugs

2019

Abstract By exploiting the chemical versatility and the high water dispersibility of α,β-poly(N-2-hydroxyethyl)D,L-aspartamide, in this work, two different polymer derivatives were synthesized for the first time. Obtained macromolecules were characterized and used to produce hydrogels exploitable for the local release of hydrophobic anticancer drugs. The first derivative, bearing pendant β-cyclodextrins, was employed to solubilize tamoxifen, chosen as a model drug, and to produce a water soluble supramolecular complex, as evidenced through tamoxifen phase solubility studies. The second derivative, bearing pendant Cyclo(Arginine-Glyicine-Asparagine-D-Phenilyalanine-Cysteine) peptide moieties…

Physicochemical and Rheological Characterization of Different Low Molecular Weight Gellan Gum Products and Derived Ionotropic Crosslinked Hydrogels

2021

A series of four different low molecular weight gellan gum products was obtained by alkaline hydrolysis with the aim to investigate the impact of the molecular weight on the rheological properties of the polysaccharide aqueous dispersions and on the physicochemical characteristics of derived ionotropic crosslinked hydrogels. In particular, thermo-rheological analysis was conducted on aqueous dispersions to study the influence of molecular weight on the thermogelation properties typical of the native polysaccharide while strain sweep experiments were conducted to establish if aqueous dispersion shows a viscoelastic behavior. The effect of different Ca2+ on the rheological properties of hydro…

Cholesterol-Inulin Conjugates for Efficient SN38 Nuclear Delivery: Nanomedicines for Precision Cancer Therapy

2022

An amphiphilic inulin-thiocholesterol conjugate (INU-Cys-TC) was strategically designed as a biodegradable core-shell nanocarrier of 7-ethyl-10-hydroxy-camptothecin (SN38) to enhance its solubility and stability in aqueous media, thus exploiting its brilliant anticancer effect. INU-Cys-TC was designed to have the hydrophilic inulin backbone (external shell) partially functionalized with hydrophobic thiocholesterol moieties (internal core) through a biodegradable disulfide bond due to cysteamine bridges. Thiocholesterol moieties impair redox-sensitive self-assembling abilities, yielding to nano-sized micelles in aqueous media capable of efficiently encapsulating a high amount of SN38 (DL = 8…

Polymeric prodrug for release of an antitumoral agent by specific enzymes.

2001

The clinical usefulness of antitumor chemotherapy has been strongly limited by the lack of specificity of most anticancer drugs, which act also against healthy cells. The aim of this work was to design, synthesize, and evaluate a macromolecular prodrug of Cytarabine, a known antitumor drug, which is a specific substrate for plasmin enzyme whose concentration is high in various kinds of tumor mass as a result of plasminogen activator secretion. alpha,beta-Poly(N-hydroxyethyl)-DL-aspartamide (PHEA), a known synthetic and biocompatible polyamino acid, was used as a drug carrier, and Cytarabine was linked to PHEA by D-Val-Leu-Lys spacer synthesized beginning from Cbz-D-Val-LeuOH dipeptide and N…

Kinetics of Molecule Transfer between Lipid Vesicles and β-Cyclodextrins

1996

Abstract We propose a calorimetric method based on the van't Hoff model of depression of the freezing temperature to investigate slow kinetics involving lipid vesicles (liposomes) and drug–β-cyclodextrin (Cyd) complexes. Some nonsteroidal antiinflammatory drugs (NSAIDs) were examined and standard phospholipid liposomes were used in our experiments. Three different kinetic processes were investigated: (a)9Transfer of drugs from water-soluble Cyd-complexes to void liposomes. (b)9Uptake of drugs from the surface of liposomes by free Cyd dissolved in the aqueous phase. (c)9Exchange of drugs from loaded to void vesicles, and the effect of free Cyd in enhancing such a transfer. Most experiments w…

New biodegradable hydrogels based on a photocrosslinkable modified polyaspartamide: synthesis and characterization

1999

Abstract α,β-Poly( N -2-hydroxyethyl)- dl -aspartamide (PHEA), a synthetic water-soluble biocompatible polymer, was derivatized with glycidyl methacrylate (GMA), in order to introduce in its structure chemical residues having double bonds and ester groups. The obtained copolymer (PHG) contained 29 mol% of GMA residues. PHG aqueous solutions at various concentrations ranging from 30 to 70 mg/ml were exposed to a source of UV rays at λ 254 nm in the presence or in the absence of N , N ′-methylenebisacrylamide (BIS); the formation of compact gel phases was observed beginning from 50 mg/ml. The obtained networks were characterized by FT-IR spectrophotometry and swelling measurements which evide…

Amphiphilic polyaspartamide copolymer-based micelles for rivastigmine delivery to neuronal cells

2012

A novel polysorbate-80 (PS(80))-attached amphiphilic copolymer comprising a hydrophilic α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) backbone and hydrophobic squalenyl-C(17) (Sq(17)) portions was synthesized and characterized; the formation of polymeric micelles was also evaluated. Rivastigmine free-base (Riv), a hydrophobic drug employed to treat Alzheimer's disease, was chosen as model drug to investigate micelle's ability to incorporate hydrophobic molecules and target them to neuronal cells. Micelle formation was studied through analyses including fluorescence spectroscopy and 2D (1)H-NMR NOESY experiments. Finally, the capacity of Riv-loaded micelles, versus free drug, to penetrat…

Synthesis, characterisation and properties of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide-graft-maleic anhydride precursors and their stimuli-responsiv…

2009

Abstract A family of poly(amino acid)-maleic anhydride hydrogels were designed and synthesized. Water soluble polymeric precursors were prepared by partially substituting the hydroxyl groups of the α,β-poly( N -2-hydroxyethyl)- dl -aspartamide backbone with maleic anhydride, so as to provide double bonds for crosslinking and carboxylic acid groups for pH and electric field responsiveness. Reaction conditions (reactive mixture composition and catalysis) were systematically varied in order to obtain PHEA–MA precursors with different and reliable graft-maleic anhydride levels. PHEA–MA precursors were characterised by titration, Nuclear Magnetic Resonance ( 1 H NMR), Fourier-Transformed Infrare…

Synthesis, mechanical and thermal rheological properties of new gellan gum derivatives

2017

New derivatives of gellan gum (GG) were prepared by covalent attachment of octadecylamine (C18- NH2) to polysaccharide backbone via amide linkage by using bis(4-nitrophenyl) carbonate (4-NPBC) as a coupling agent. The effect of the alkyl chain grafted onto hydrophilic backbone of high molecular weight GG was investigated in terms of physicochemical properties and ability of new derivatives to form hydrogels. A series of hydrogels was obtained in solutions with different kind and concentration of ions and their stability and mechanical properties were evaluated. The obtained derivatives resulted soluble at temperature lower than starting GG and physicochemical properties of obtained hydrogel…

Synthesis and evaluation of thermo-rheological behaviour and ionotropic crosslinking of new gellan gum-alkyl derivatives.

2018

Abstract This paper reports the synthesis and the physicochemical characterization of two series of gellan gum (GG) derivatives functionalized with alkyl chains with different number of carbon, from 8 to 18. In particular, low molecular weight gellan gum samples with 52.6 or 96.7 kDa, respectively, were functionalized with octylamine (C8), dodecylamine (C12) and octadecylamine (C18) by using bis(4-nitrophenyl) carbonate (4-NPBC) as a coupling agent. Thermo-rheological and ionotropic crosslinking properties of these gellan gum-alkyl derivatives were evaluated and related to the degree of derivatization in alkyl chains. Results suggested as length and degree of derivatization differently infl…

In situ forming hydrogels of hyaluronic acid and inulin derivatives for cartilage regeneration.

2014

An in situ forming hydrogel obtained by crosslinking of amino functionalized hyaluronic acid derivatives with divinylsulfone functionalized inulin (INU-DV) has been here designed and characterized. In particular two hyaluronic acid derivatives bearing respectively a pendant ethylenediamino (EDA) portion (HA-EDA) and both EDA and octadecyl pendant groups (HA-EDA-C18) were crosslinked through an azo-Michael reaction with INU-DV. Gelation time and consumption of DV portions have been evaluated on hydrogel obtained using HA-EDA and HA-EDA-C18 derivatives with a concentration of 3% w/v and a ratio 80/20 w/w respect to the crosslinker INU-DV. The presence of pendant C18 chains improves mechanical…

Mechanical Characterization of Polysaccharide/polyaminoacid Hydrogels as Potential Scaffolds for Tissue Regeneration

2011

The mechanical properties of hydrogel scaffolds based on hyaluronic acid (HA) that were chemically crosslinked with α,β-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-D,L-aspartamide (PHEA-EDA) were investigated. Variation of these properties as a function of three different PHEA-EDA amounts used to crosslink HA has been related to the reaction efficiency evaluated using a colorimetric assay. Moreover, the amount of unreacted amino groups that was still present in the hydrogels was related to the attachment behavior of human dermal fibroblasts to the hydrogel surface. The mechanical data and biological results suggest the suitability of the investigated hydrogels as scaffolds for the regener…

Developing Antibiofilm Fibrillar Scaffold with Intrinsic Capacity to Produce Silver Nanoparticles

2022

The development of biomedical systems with antimicrobial and antibiofilm properties is a difficult medical task for preventing bacterial adhesion and growth on implanted devices. In this work, a fibrillar scaffold was produced by electrospinning a polymeric organic dispersion of polylactic acid (PLA) and poly(α,β-(N-(3,4-dihydroxyphenethyl)-L-aspartamide-co-α,β-N-(2-hydroxyethyl)-L-aspartamide) (PDAEA). The pendant catechol groups of PDAEA were used to reduce silver ions in situ and produce silver nanoparticles onto the surface of the electrospun fibers through a simple and reproducible procedure. The morphological and physicochemical characterization of the obtained s…

Solid lipid nanoparticles containing tamoxifen characterization and in vitro antitumoral activity.

2005

Solid lipid nanoparticles (SLNs) containing tamoxifen, a nons- teroidal antiestrogen used in breast cancer therapy, were prepared by microemulsion and precipitation techniques. Tamoxifen loaded SLNs seem to have dimensional properties useful for parenteral administration, and in vitro plasmatic drug release studies demon- strated that these systems are able to give a prolonged release of the drug in the intact form. Preliminary study of antiproliferative ac- tivity in vitro, carried out on MCF-7 cell line (human breast cancer cells), demonstrated that SLNs, containing tamoxifen showed an antitumoral activity comparable to free drug. The results of char- acterization studies and of in vitro …

Ocular tolerability and in vivo bioavailability of poly(ethylene glycol) (PEG)-coated polyethyl-2-cyanoacrylate nanosphere-encapsulated acyclovir.

2001

Acyclovir-loaded polyethyl-2-cyanoacrylate (PECA) nanospheres were prepared by an emulsion polymerization process in the micellar phase and characterized. The influence of the presence of nonionic surfactant as well as other substances [i.e., 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and poly(ethylene glycol) (PEG)], on formulation parameters and loading capacity was investigated. In particular, the presence of PEG resulted in an increase of mean size and size distribution. To obtain PEG-coated PECA nanospheres with a mean size of200 nm, Pluronic F68 at concentrations1.5% (w/v) should be used during preparation. The presence of PEG also resulted in a change in zeta potential, from -25…

DIFFERENTIAL SCANNING CALORIMETRY STUDY ON DRUG RELEASE FROM AN INULIN-BASED HYDROGEL AND ITS INTERACTION WITH A BIOMEMBRANE MODEL:pH AND LOADING EFF…

2008

Inulin has been derivatized with methacrylic anhydride (MA) and succinic anhydride (SA) to obtain a methacrylated/succinilated derivative (INU-MA-SA) able to produce a pH sensitive hydrogel after UV irradiation. The hydrogel was characterized and loaded with diflunisal (10.4, 17 and 24%, w/w) chosen as a model drug. The drug release from INU-MA-SA-based hydrogel to a biomembrane model made by unilamellar vesicles of dimyristoylphosphatidyl-choline (DMPC) was investigated at pH 4.0 and 7.4 by differential scanning calorimetry (DSC) that appears to be a suitable technique to follow the transfer kinetics of a drug from a controlled release system to a biomembrane model. The drug release from t…

Smart copolymer coated SPIONs for colon cancer chemotherapy

2019

Human colon cancer is one of the higher aggressive solid tumors, whose high mortality, much like many other solid tumors, results from metastasis formation. To reduce this high mortality, more effective chemotherapy, allowing a specific tumor accumulation and an efficient early-stage medical imaging as well, are still needed. At this regard, stimuli-responsive nanocarriers for anticancer drug delivery are promising strategy in cancer therapy. For this purpose, a dual targeted redox-responsive drug delivery system, prepared by coating superparamagnetic nanoparticles (SPIONs) with the amphiphilic copolymer INU-LA-PEG-FA and loading doxorubicin (DOXO-SPIONs) was investigated as tool for solid …

Synthesis, characterization and foaming of PHEA-PLLA, a new graft copolymer for biomedical engineering

2014

Abstract In this study a chemical grafting procedure was set up in order to link high molecular weight poly L-lactic acid (PLLA) chains to the hydrophilic α,β-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) backbone. A graft copolymer named PHEA-g-PLLA (or simply PHEA–PLLA) was obtained bearing a degree of derivatization of 1.0 mol.% of PLLA as grafted chain. This new hybrid derivative offers both the opportune crystallinity necessary for the production of scaffolds trough a thermally induced phase separation (TIPS) technique and the proper chemical reactivity to perform further functionalizations with bio-effectors and drugs. PHEA–PLLA porous scaffolds for tissue engineering applications were…

Poly(hydroxyethylaspartamide) derivatives as colloidal drug carrier systems

2003

Abstract Poly(hydroxyethylaspartamide) (PHEA) derivatives bearing at the polyaminoacidic backbone poly(ethyleneglycol) (2000 or 5000 Da) or both poly(ethyleneglycol) and hexadecylalkylamine as pendant moieties were investigated as polymeric colloidal drug carriers. The ability of the PHEA derivatives to solubilize hydrophobic drugs was investigated using paclitaxel, amphotericin B and methotrexate. The results demonstrated that the drug solubility depends on both macromolecule composition and drug physicochemical properties. In particular, PEG/hexadecylalkylamine co-grafting increased significantly the solubilization properties of PHEA for the considered drugs while the conjugation of PEG o…

Using Polymeric Scaffolds for Vascular Tissue Engineering

2014

With the high occurrence of cardiovascular disease and increasing numbers of patients requiring vascular access, there is a significant need for small-diameter (<6 mm inner diameter) vascular graft that can provide long-term patency. Despite the technological improvements, restenosis and graft thrombosis continue to hamper the success of the implants. Vascular tissue engineering is a new field that has undergone enormous growth over the last decade and has proposed valid solutions for blood vessels repair. The goal of vascular tissue engineering is to produce neovessels and neoorgan tissue from autologous cells using a biodegradable polymer as a scaffold. The most important advantage of …

Medicated hydrogels of hyaluronic acid derivatives for use in orthopedic field.

2013

Physical hydrogels have been obtained from hyaluronic acid derivatized with polylactic acid in the presence or in the absence of polyethylene glycol chains. They have been extemporarily loaded with antibacterial agents, such as vancomycin and tobramycin. These medicated hydrogels have been used to coat titanium disks (chosen as simple model of orthopedic prosthesis) and in vitro studies in simulated physiological fluid have been performed as a function of time and for different drug loading and polymer concentration values. Sterilization process performed on the hydrogels does not change their rheological behavior and release properties as well as the chemical structure of starting copolyme…

Chemical stiffening of constructs between polymeric microparticles based on a hyaluronic acid derivative and mesenchymal stem cells: rheological and …

2018

Hyaluronan alkyl derivatives-based electrospun membranes for potential guided bone regeneration: Fabrication, characterization and in vitro osteoindu…

2020

Item does not contain fulltext The aim of the work was to determine the effects of the chemical functionalization of hyaluronic acid (HA) with pendant aliphatic tails at different lengths and free amino groups in terms of chemical reactivity, degradation rate, drug-eluting features, and surface properties when processed as electrospun membranes (EM) evaluating the osteoinductive potential for a possible application as guided bone regeneration (GBR). To this end, a series of HA derivatives with different aliphatic tails (DD-Cx mol% ≈ 12.0 mol%) and decreasing derivatization of free amino groups (DD(EDA) mol% from 70.0 to 30.0 mol%) were first synthesized, namely Hn. Then dexamethasone-loaded…

Polymeric drug delivery micelle-like nanocarriers for pulmonary administration of beclomethasone dipropionate

2017

In this paper, the potential of novel polymeric micelles as drug delivery systems for Beclomethasone Dipropionate (BDP) administration into the lung is investigated. These nanostructures are obtained starting from α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA), which was subsequently functionalized with O-(2-aminoethyl)-O’-methylpolyethylenglycole (PEG2000), ethylenediamine (EDA) and lipoic acid (LA), obtaining PHEA-PEG2000-EDA-LA graft copolymer. Empty and drug-loaded micelles possess adequate chemical-physical characteristics for pulmonary administration such as spherical shape, slightly positive surface charge and mean size of about 200 nm. Besides, BDP-loaded micelles, obtained …

Production of polymeric micro- and nanostructures with tunable properties as pharmaceutical delivery systems

2020

Abstract The production of novel graft copolymers based on poly-e-caprolactone (PCL) and polyaspartamide are useful to realize structures for potential biomedical applications. Here, the synthesis of pegylated PCL/polyhydroxyethyl aspartamide (PHEA) graft copolymers (PHEA-g-SUCC-PCL-g-PEG) with tunable composition, was achieved by followpling a synthetic strategy that involved first the grafting of preformed PCL on PHEA backbone, then polyethylen glycol (PEG), by using 1,1′-carbonyldiimidazole (CDI) to speed up the condensation reaction. Graft copolymers with a Derivatization Degree (DD) in PCL ranging between 1.1 and 4.4 mol% were obtained, and processable with different technologies for t…

Ferulic Acid-Loaded Lipid Nanostructures as Drug Delivery Systems for Alzheimers Disease: Preparation, Characterization and Cytotoxicity Studies

2009

PHEA-graft-polybutylmethacrylate copolymer microparticles for delivery of hydrophobic drugs.

2012

Abstract Polymeric microparticles encapsulating two model hydrophobic drugs, beclomethasone dipropionate (BDP) and flutamide (FLU) were prepared by using the high pressure homogenization-solvent evaporation method starting from a oil-in-water emulsion. For the preparation of polymeric microparticles a α,β-poly(N-2-hydroxyethyl)- d , l -aspartamide (PHEA) graft copolymer with comb like structure was properly synthesized via grafting from atom transfer radical polymerization (ATRP) technique, by using two subsequent synthetic steps. In the first step a polymeric multifunctional macroinitiator was obtained by the conjugation of a proper number of 2-bromoisobutyryl bromide (BIB) residues to the…

Nanosystem for diagnosis and photothermal treatment of tumors

2022

The invention relates to a nanosystem for the diagnosis, image-guided treatment of tumors and monitoring of the tumor microenvironment. The nanosystem is a contrast agent comprising a polymer shell based on a hyaluronic acid nanogel, super-parameg-netic iron oxide nanoparticles (SPIONs) and carbon nanoparticles (CDs).

Construction and evaluation of sponge scaffolds from hyaluronic acid derivatives for potential cartilage regeneration

2020

A two or one pot synthesis has been used for the reaction of hyaluronic acid (HA) with octadecylamine (C-18) and hydrazine (Hy). In both cases, the chemical derivatization involved primary hydroxyl groups of hyaluronic acid and not its carboxyl groups, whose presence is important for receptor interaction. In this way, Hy-HA-C-18 derivatives have been obtained with appropriate hydrophobic and hydrophilic character. Their ability to form homogeneous physical hydrogels has been evaluated as well as the possibility to obtain porous sponges through salt leaching technology. Sponges showing the highest porosity, potentially compatible with cell entrapment, have been characterized with regard to t…

Bisphosphonate-polyaspartamide conjugates as bone targeted drug delivery systems.

2015

Poly-hydroxy-aspartamide was used as a backbone to synthesize bisphosphonate derivatives thus achieving macromolecular carriers to be potentially used as targeting agents for bone drug delivery. Molecules bearing bisphosphonate groups, such as aminobisphosphonate (ABP) and neridronate (NRD), have been conjugated to polyaspartamide (α,β-poly(N-2-hydroxyethyl)-dl-aspartamide, PHEA), with or without a spacer (succinic acid or 6-aminocaproic acid) thus obtaining PHEA-succinate-ABP and PHEA-caproylcarbamate-ABP and PHEA-ABP and PHEA-NRD, respectively. Bisphosphonate-polymer conjugates were physico-chemically characterized using size exclusion chromatography and 1H-NMR; and their in vitro and e…

PHEA-graft-polymethacrylate supramolecular aggregates for protein oral delivery

2013

Abstract Salmon calcitonin (sCT) is characterized by a poor oral availability. A new copolymer, β-poly(N-2-hydroxyethyl)-graft-{N-2-ethylene[2-poly(methacrylic acid sodium salt)isobutyrate]}- d , l -aspartamide (PHEA-IB-p(MANa + )), was designed for the oral administration of sCT through the formation of supramolecular aggregates (SAs) based on electrostatic interactions. Several sCT/PHEA-IB-p(MANa + ) weight ratios were characterized by turbidimetry, DLS, zeta potential, and microscopy analysis. After the incubation of sCT/PHEA-IB-p(MANa + ) complex with digestive enzymes, 10% (w/w) of loaded sCT was released in the native form. In vitro investigation was carried out to determine the copol…

Evaluation of thermoresponsive properties and biocompatibility of polybenzofulvene aggregates for leuprolide delivery

2012

Abstract In this study, a polybenzofulvene derivative named poly-6-MOEG-9-BF3k, was evaluated as polymeric material for the production of injectable thermoresponsive nano-aggregates able to load low molecular weight peptidic drug, like the anticancer leuprolide. Thermoresponsive behavior of poly-6-MOEG-9-BF3k was studied in aqueous media by evaluating scattering intensity variations by means of DLS in function of temperature. Zeta potential measurements and SEM observations were also carried out. Moreover, critical aggregation temperature of the poly-6-MOEG-9-BF3k polymer was evaluated by pyrene fluorescence analysis. Then, the ability of prepared thermoresponsive aggregates to protect this…

Biodegradable and pH-sensitive hydrogels for potential colon-specific drug delivery: Characterization and in vitro release studies

2008

A novel pH-sensitive and biodegradable composite hydrogel, based on a methacrylated and succinic derivative of dextran, named Dex-MA-SA, and a methacrylated and succinic derivative of alpha,beta-poly( N-2-hydroxyethyl)- DL-aspartamide (PHEA), named PHM-SA, was produced by photocross-linking. The goal was to obtain a colon-specific drug delivery system, exploiting both the pH-sensitive behavior and the colon-specific degradability. The hydrogel prepared with a suitable ratio between the polysaccharide and the polyaminoacid was characterized regarding its swelling behavior in gastrointestinal simulated conditions, chemical and enzymatic degradability, interaction with mucin, and cell compatib…

Realization of polyaspartamide-based nanoparticles and in vivo lung biodistribution evaluation of a loaded gucocorticoid after aerosolization in mice

2016

Abstract In this study, novel polymeric nanoparticles (NPs) were developed and their potential as carriers for beclomethasone dipropionate (BDP) into the lung after aerosolization was demonstrated by in vivo studies in mice. In particular, these NPs were obtained starting from two polyaspartamide-based copolymers which were synthesized by chemical reaction of α,β-poly(N-2-hydroxyethyl)- dl -aspartamide (PHEA) and its pegylated derivative (PHEA-PEG2000) with poly(lactic acid) (PLA). To obtain nanosized particles, the high pressure homogenization (HPH)—solvent evaporation method was followed by using an organic phase containing both PHEA-PLA and PHEA-PEG2000-PLA (at a weight ratio equal to 1:…

Hepatocyte-targeted fluorescent nanoparticles based on a polyaspartamide for potential theranostic applications

2015

Abstract Here, the synthesis of a galactosylated amphiphilic copolymer bearing rhodamine (RhB) moieties and its use for the preparation of polymeric fluorescent nanoparticles for potential applications in therapy and diagnosis are described. To do this, firstly, a fluorescent derivative of α,β-poly( N -2-hydroxyethyl)- d , l -aspartamide (PHEA) was synthesized by chemical reaction with RhB, and with polylactic acid (PLA), to obtain PHEA-RhB-PLA. Then, the derivatization of PHEA-RhB-PLA with GAL-PEG-NH 2 allows obtaining PHEA-RhB-PLA-PEG-GAL copolymer, with derivatization degrees in -PLA and -PEG-GAL equal to 1.9 mol% and 4.5 mol%, respectively. Starting from this copolymer, liver-targeted f…

Ultrafast Interface Charge Separation in Carbon Nanodot-Nanotube Hybrids

2021

Carbon dots are an emerging family of zero-dimensional nanocarbons behaving as tunable light harvesters and photoactivated charge donors. Coupling them to carbon nanotubes, which are well-known electron acceptors with excellent charge transport capabilities, is very promising for several applications. Here, we first devised a route to achieve the stable electrostatic binding of carbon dots to multi- or single-walled carbon nanotubes, as confirmed by several experimental observations. The photoluminescence of carbon dots is strongly quenched when they contact either semiconductive or conductive nanotubes, indicating a strong electronic coupling to both. Theoretical simulations predict a favo…

A Hydrogel Based on a Polyaspartamide: Characterization and Evaluation of In-vivo Biocompatibility and Drug Release in the Rat

1997

Abstract This paper deals with the characterization of a new microparticulate hydrogel obtained by gamma irradiation of α,β-poly[N-(2-hydroxyethyl)-dl-aspartamide] (PHEA). When enzymatic digestion of PHEA hydrogel was evaluated using various concentrations of pepsin and α-chymotrypsin no degradation occurred within 24 h. In-vivo studies showed that this new material is biocompatible after oral administration to rats. PHEA hydrogel was also studied as a system for delivery of diflunisal, an anti-inflammatory drug. In-vitro release studies in simulated gastrointestinal juice (pH 1 or 6.8) showed that most of the drug was released at pH 6.8. In-vivo studies indicated that diflunisal-loaded PHE…

Near-Infrared, Light-Triggered, On-Demand Antiinflammatories and Antibiotics Release by Graphene Oxide/Elecrospun PCL Patch for Wound Healing

2019

Very recently, significant attention has been focused on the adsorption and cell adhesion properties of graphene oxide (GO), because it is expected to allow high drug loading and controlled drug release, as well as the promotion of cell adhesion and proliferation. This is particularly interesting in the promotion of wound healing, where antibiotics and anti-inflammatories should be locally released for a prolonged time to allow fibroblast proliferation. Here, we designed an implantable patch consisting of poly(caprolactone) electrospun covered with GO, henceforth named GO&ndash

Microgels of polyaspartamide and poly(ethylene glycol) derivatives obtained by γ-irradiation

2002

Abstract The copolymer PHG based on α , β -poly( N -2-hydroxyethyl)- dl -aspartamide (PHEA) functionalized with glycidyl methacrylate has been exposed in aqueous solution to a γ -ray source at different irradiation doses (2, 2.5 and 3.5 kGy), alone or in combination with poly(ethylene glycol)dimethacrylate (PEGDMA) or poly(ethylene glycol)diacrylate (PEGDA). The irradiation produces microgel systems that have been characterized by viscosity measurements. Lyophilization of microgels gives rise to samples able to swell instantaneously in water whereas their treatment with acetone produces swellable microparticles that have been characterized.

Curcumin entrapped into lipid nanosystems inhibits neuroblastoma cancer cell growth and activates Hsp70 protein

2010

Curcumin is a natural anti-cancer compound utilized on a wide variety of human cancer cell lines and animal carcinogenesis models. However, its clinical application has been limited for its minimal systemic bioavailability. Nanoparticle-based drug delivery approaches have the potential for rendering hydrophobic molecules such as curcumin dispersible in aqueous media, thus overtaking the limits of its poor solubility. In this paper, we reported the preparation and chemical-physical characterization of Nanostructured Lipid Carriers (NLC) containing curcumin, based on Imwitor, Compritol or Precirol as lipid matrix. By in vitro experiments, we have demonstrated that these nano-systems are able …

SYNTHESIS AND CHARACTERIZATION OF POLYAMINOACIDIC POLYCATIONS FOR GENE DELIVERY

2005

The properties as non viral gene vector of a protein-like polymer, the alpha,beta-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) were exploited after its derivatization with 3-(carboxypropyl)trimethyl-ammonium chloride (CPTA) as molecule bearing a cationic group, in order to obtain stable polycations able to condense DNA. PHEA was firstly functionalized with aminic pendant groups by reaction with ethylenediamine (EDA) obtaining the alpha,beta-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-d,l-aspartamide (PHEA-EDA) copolymer. We demonstrated that polymer functionalization degree is easily modulable by varying reaction conditions, so allowing to produce two PHEA-EDA derivatives at different mo…

Electrospinning of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide-graft-polylactic acid to produce a fibrillar scaffold

2010

Abstract α,β-Poly( N -2-hydroxyethyl)- dl -aspartamide grafted with polylactic acid (PHEA- g -PLA) is a biocompatible and biodegradable amphiphilic copolymer that has been already employed to prepare a drug delivery system. In this study we have prepared for the first time a fibrillar scaffold from PHEA- g -PLA by the electrospinning of a solution of this copolymer in a mixture of N , N -dimethyl formamide (DMF) and acetone (80:20 vol/vol). The average diameter and the morphology of electrospun fibers were detected by scanning electron microscopy. Chemical degradation studies in phosphate buffer solution pH 7.4 have been performed until 15 days in order to obtain a preliminary information a…

COMPARATIVE-STUDY ON INCLUSION-COMPOUNDS OF 4-BIPHENYLACETIC ACID WITH BETA-CYCLODEXTRIN, HYDROXYPROPYLATED-BETA-CYCLODEXTRINS, AND METHYLATED-BETA-C…

1994

AbstractThe inclusion behavior of Hydroxypropyl-β-Cyclodextrin (HP-β-Cyd) and of methylated-β-Cyclodextrins, heptakis-(2,6-di-O-methyl)-β-Cyclodextrin (DM-β-Cyd) and heptakis-(2,3,6-tri-O-methyl)-β-Cyclodextrin (TM-β-Cyd), in solution and solid state was compared with that of natural β-Cyclodextrin (β-Cyd) using an anti-inflammatory drug, 4-biphenylacetic acid (BPAA), as a guest molecule. The solubility of BPAA with β-Cyd and β-Cyd derivatives in aqueous solution were determined. Stability constants were calculated by phase solubility method at various pH values and temperatures. The formation of inclusion complexes with β-Cyd and β-Cyd derivatives in the solid slate were confirmed by infra…

Polysaccharide/polyaminoacid composite scaffolds for modified DNA release.

2009

Abstract In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently crosslinked with α,β-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)- d , l -aspartamide (PE), have been prepared and characterized as local gene delivery systems. In particular, HA/PE scaffolds have been loaded with PE/DNA interpolyelectrolyte complexes, employing PE as a macromolecular crosslinker for HA and as a non-viral vector for DNA. In vitro studies showed that HA/PE films and sponges have high compatibility with human dermal fibroblasts and they give a sustained DNA release, whose trend can be easily tailored by varying the crosslinking ratio between HA and PE. Electrophoresis analysi…

Inhalable nano into micro dry powders for ivacaftor delivery: The role of mannitol and cysteamine as mucus-active agents.

2020

In this paper the innovative approach of Nano into micro (NiM9 was developed to produce Nanoparticles loaded Ivacaftor to incorporate into mannitol or mannitol/cysteamine micromatrices for drug pulmonary administration in CF. Nanoparticles composed by a mixture of two polyhydrohydroxyethtylaspartamide copolymers containing a loading of Ivacaftor of 15.5 % w/w were produced. These Nanoparticles were incorporated into microparticles to obtain NiM that were characterized in terms of size and size distribution, interaction with CF-AM by rheological and turbidimetric studies as well as by aerodynamic diameter measurements. Finally the activity of Ivacaftor into these NiM was evaluated by in vitr…

Polymeric nanoparticles for siRNA delivery: Production and applications

2017

Gene therapy through the use of siRNA and a polymeric carrier are becoming an efficient therapeutic option to conventional pharmaceutical formulations for the treatment of deadly diseases, such as cancer, pulmonary, ocular and neurodegenerative diseases. However, several considerations regarding the stability, formulation, and efficacy have to be faced up until these systems could be considered to be a marketable pharmaceutical products for to extend siRNA application to clinical practice. This review is focused on the key challenges of siRNA therapeutics, with special attention on the faced obstacles and on the formulation-related difficulties, providing a list of requirements needed for o…

Microfluidic production of hyaluronic acid derivative microfibers to control drug release

2016

"Available online 4 July 2016"

Polyaspartamide-Doxorubicin Conjugate as Potential Prodrug for Anticancer Therapy

2015

Purpose To synthesize a new polymeric prodrug based on ?,?- poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-d,l-aspartamide copolymer bearing amine groups in the side chain (PHEA-EDA), covalently linked to the anticancer drug doxorubicin and to test its potential application in anticancer therapy. Methods The drug was previously derivatized with a biocompatible and hydrophilic linker, leading to a doxorubicin derivative highly reactive with amino groups of PHEA-EDA. The PHEAEDA- DOXO prodrug was characterized in terms of chemical stability. The pharmacokinetics, biodistribution and cytotoxicity of the product was investigated in vitro and in vivo on human breast cancer MCF-7 and T47D cell lin…

Hyaluronan-coated polybenzofulvene brushes as biomimetic materials

2016

Hyaluronic acid (HA) forms pericellular coats in many cell types that are involved in the early stages of cell adhesion by interacting with the CD44 receptor. Based on the largely recognized overexpression of the CD44 receptor in tumor tissues, a polybenzofulvene molecular brush has been enveloped into hyaluronan shells to obtain a tri-component polymer brush (TCPB) composed of intrinsically fluorescent backbones bearing nona(ethylene glycol) arms terminated with low molecular weight HA macromolecules. The nanoaggregates obtained in TCPB water dispersions were characterized on the basis of dimensions, zeta potential, and in vitro cell toxicity. This biomimetic multifunctional material beari…

CROSSLINKED HYALURONAN WITH A PROTEIN-LIKE POLYMER: NOVEL BIORESORBABLE FILMS FOR BIOMEDICAL APPLICATIONS

2007

In this work, novel hydrogel films based on hyaluronan (HA) chemically crosslinked with the alpha,beta-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-D,L-aspartamide (PHEA-EDA) were produced by solution casting method. The goal was to exploit both the biological key role of HA in tissue repair and regeneration, and the versatility of a synthetic protein-like polymer as the PHEA-EDA, in order to obtain biomaterials with physicochemical and biological properties suitable for a clinical use. By varying the molar ratio between the PHEA-EDA amino groups and HA carboxyl groups, three different films were obtained and characterized. Particularly FTIR, swelling, hydrolysis, and enzymatic degradatio…

Reaction of 2-acetyltetralone with some esters of benzoic acid

1986

In order to investigate the pharmacological screening of a number of pyran-4-ones their synthesis by cyclization with sulphuric acid of the corresponding 1,3,5-triketones has been carried out with high yields. In the course of preparation of the latter the reaction of 2-acetyltetralone with some esters of benzoic acid derivatives has been studied and in particular, for a number of them, an interesting nucleophilic substitution of a chlorine atom with an alkoxy group on a benzenic nucleus has been evidenced.

Improvements in Rational Design Strategies of Inulin Derivative Polycation for siRNA Delivery.

2016

The advances of short interfering RNA (siRNA)-mediated therapy provide a powerful option for the treatment of many diseases, including cancer, by silencing the expression of targeted genes involved in the progression of the pathology. On this regard, a new pH-responsive polycation derived from inulin, Inulin-g-imidazole-g-diethylenetriamine (INU-IMI-DETA), was designed and employed to produce INU-IMI-DETA/siRNA "Inulin COmplex Nanoaggregates" (ICONs). The experimental results showed that INU-IMI-DETA exhibited strong cationic characteristics and high solubility in the pH range 3-5 and self-aggregation triggered by pH increase and physiological salt concentration. INU-IMI-DETA showed as well…

Novel hydrogels based on a polyasparthydrazide. Synthesis and characterization

2000

α,β-polyasparthydrazide (PAHy), a synthetic water-soluble biocompatible polymer, was chemically crosslinked with ethyleneglycol diglycidylether (EGDGE), in order to obtain water swellable microparticies. These were characterized by means of FT-IR spectrophotometry and by means of particle size distribution analysis. The mean pore size of the prepared gels as various crosslinking ratios and the fractal dimensions were determined by light scattering measurements. Swelling measurements gave evidence of the high affinity of PAHy-EGDGE microparticles towards aqueous media at different pH values. The physical state of the prepared networks was evaluated by means of X-rays diffractometry and therm…

A Nanoparticulate Drug-Delivery System for Rivastigmine: Physico-Chemical and in vitro Biological Characterization

2007

The preparation and characterization of surface-PEGylated polymeric nanoparticles are described. These systems were obtained by UV irradiation of PHM and PHM-PEG 2000 as an inverse microemulsion, using an aqueous solution of the PHM/PHM-PEG 2000 copolymer mixture as the internal phase and triacetin saturated with water as the external phase, and characterized by dimensional analysis, zeta-potential measurements and XPS. in vitro biological tests demonstrated their cell compatibility and their ability to escape from phagocytosis. Rivastigmine was encapsulated into the nanoparticle structure and drug-release profiles from loaded samples were investigated in PBS at pH = 7.4 and human plasma.

Effect of?-cyclodextrin complexation on the photohaemolitic activity induced by Ketoprofen and Naproxen sensitization

1993

Red blood cell lysis photosensitized by two non-steroidal anti-inflammatory drugs Naproxen (NAP) and Ketoprofen (KPF) was investigated in the presence of β-cyclodextrin (β-Cyd). The photohaemolysis was inhibited by the addition of β-Cyd both for NAP and, to a lesser extent, for KPF. The protective action was found only in a restricted range of concentration of β-Cyd. Higher amounts of β-Cyd interfered with the resistance of the cell to the osmotic shock induced by the photosensitization process. The complexing action of β-Cyd was ascertained through UV-vis absorption spectroscopy, induced circular dichroism and emission spectroscopy. The isolated complexes Naproxen-β-Cyd (NAP-β-Cyd) and Ket…

Microfluidic Fabrication of Physically Assembled Nanogels and Micrometric Fibers by Using a Hyaluronic Acid Derivative

2017

The employ of a hyaluronic acid (HA) derivative, bearing octadecyl (C18) and ethylenediamine (EDA) groups, for microfluidic fabrication of nanogels and microfibers is reported in this study. Two HA-EDA-C18 derivatives (125 and 320 kDa) having ionic strength sensitive properties are synthesized and characterized. The control of the rheological properties of HA-EDA-C18 aqueous dispersions by formation of inclusion complexes with hydroxypropyl-β-cyclodextrins (HPCD) is described. Reversibility of C18/HPCD complexation and physical crosslinking is detected in media with different ionic strength through oscillation frequency tests. HA-EDA-C18 125 kDa is employed for nanogel fabrication. Control …

Polyaspartamide-based nanoparticles loaded with fluticasone propionate and the in vitro evaluation towards cigarette smoke effects

2017

This paper describes the evaluation of polymeric nanoparticles (NPs) as a potential carrier for lung administration of fluticasone propionate (FP). The chosen polymeric material to produce NPs was a copolymer based on α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) whose backbone was derivatised with different molecules, such as poly(lactic acid) (PLA) and polyethylenglycol (PEG). The chosen method to produce NPs from PHEA-PLA-PEG2000 was the method based on high-pressure homogenization and subsequent solvent evaporation by adding Pluronic F68 during the process and trehalose before lyophilisation. Obtained colloidal FP-loaded NPs showed a slightly negative surface charge and nanometric d…

Polyaspartamide-polylactide electrospun scaffolds for potential topical release of Ibuprofen.

2012

In this work, the production and characterization of electrospun scaffolds of the copolymer α,β-poly(N-2-hydroxyethyl)-DL-aspartamide-graft-polylactic acid (PHEA-g-PLA), proposed for a potential topical release of Ibuprofen (IBU), are reported. The drug has been chemically linked to PHEA-g-PLA and/or physically mixed to the copolymer before electrospinning. Degradation studies have been performed as a function of time in Dulbecco phosphate buffer solution pH 7.4, for both unloaded and drug-loaded scaffolds. By using an appropriate ratio between drug physically blended to the copolymer and drug-copolymer conjugate, a useful control of its release can be obtained. MTS assay on human dermal fi…

Engineering Oral Mucosal Polymeric Patches for Treatment of Childhood-Onset Schizophrenia

Mesoporous silicate as matrix for drug delivery systems of non-steroidal antinflammatory drugs

2002

Publisher Summary The suitability of a mesoporous silicate matrix as a drug-delivery system has been evaluated using different nonsteroid anti-inflammatory agents as model drugs. This type of matrix can trap the bioactive agents by a soaking procedure and then release them in conditions mimicking the biological fluids. The high affinity of these matrices for water makes them potentially biocompatible. A matrix impregnated with diflunisal can offer a good potential as a system for the controlled drug release. In fact, only 20% of the drug is released at the gastric level allowing, in this way, the reduction of side effects related to the oral administration of nonsteroidal anti-inflammatory …

Influence of different parameters on drug release from hydrogel systems to a biomembrane model. Evaluation by differential scanning calorimetry techn…

2000

A comparative study on the drug release capacity of four water swellable polymeric systems was carried out by differential scanning calorimetry (DSC). The polymeric systems chosen were alpha,beta-polyaspartahydrazide (PAHy) crosslinked by glutaraldehyde (GLU) (PAHy-GLU) or by ethyleneglycoldiglycidylether (EGDGE), (PAHy-EGDGE), polyvinylalcohol (PVA) crosslinked by glutaraldehyde (PVA-GLU) and alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) by gamma irradiation (PHEA-gamma matrices). The degree of crosslinking for PAHy-GLU, PAHy-EGDGE and PVA-GLU samples was about 0.4 and 0.8. These hydrogels were characterized as free of drugs and were loaded with diflunisal (DFN) (approximately 2.5%…

PHEA‐PLLA: A New Polymer Blend For Tissue Engineering Applications

2011

One of most important features that a material should have in order to be utilized for tissue engineering applications is its biocompatibility and its chemical surface. These properties are required for a high degree of cell adhesion on the scaffold. Poly‐L‐lactid acid (PLLA) is a biocompatible synthetic polymer approved by the Food and Drug Administration for human clinical applications. It has been largely employed, in the last years, as a constituent of surgical and implantable devices. PHEA is a biocompatible water‐soluble synthetic polymer, with a protein‐like structure, whose use as a drug carrier and as starting material for many other biomedical and pharmaceutical applications has b…

BRAIN-TARGETED SOLID LIPID NANOPARTICLES CONTAINING RILUZOLE: PREPARATION, CHARACTERIZATION AND BIODISTRIBUTION

2009

Aim: Developments within nanomedicine have revealed a great potential for drug delivery to the brain. In this study nanoparticulate systems as drug carriers for riluzole, with sufficiently high loading capacity and small particle size, were prepared to a reach therapeutic drug level in the brain. Materials & method: Solid lipid nanoparticles containing riluzole have great potential as drug-delivery systems for amyotrophic lateral sclerosis and were produced by using the warm oil-in-water microemulsion technique. The resulting systems obtained were approximately 88 nm in size and negatively charged. Drug-release profiles demonstrated that a drug release was dependent on medium pH. Biodi…

Rheological characterization and release properties of inulin-based hydrogels

2012

Abstract In the present study the rheological properties of hydrogels obtained through UV irradiation of an aqueous solution of methacrylated inulin (INUMA) alone or in the presence of four different crosslinkers, have been recorded as a function of irradiation time, at two different wavelengths (320 and 365 nm) and fixed frequency and amplitude by oscillatory experiments. Each hydrogel has been analyzed by measurements of the frequency-dependency of the elastic modulus, G ′, in the linear viscoelastic region. The amount of polymeric chains giving an elastic response has been correlated to the chemical nature of the crosslinker used together with INUMA. Finally the release properties of the…

In vitro evaluation of glycol chitosan based formulations as oral delivery systems for efflux pump inhibition.

2017

Recently, we have reported that glycol chitosan (GCS) was able to reverse the P- glycoprotein (P-gp) efflux pump. The objective of the present study was to evaluate the potential of two GCS-based dosage forms (aqueous solution or nanoparticle suspension) for oral administration of the P-gp substrate Rho-123. A further aim of the present study was to assess the effect of the glycol chitosan-4-thiobutylamidine thiomer (GCS-TBA) on P-gp activity considering that the corresponding thiomer of chitosan series is a well-known P-gp inhibitor. Pre-treatment of Caco-2 cell monolayer with a GCS solution or GCS-based nanoparticles increased the absorptive transport of Rho-123 across the monolayer of 1.…