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

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…

SYNTHESIS AND CHARACTERIZATION OF NEW AMPHIPHILIC COPOLYMERS BASED ON A POLY(HYDROXYETHYL)-D,L-ASPARTAMIDE (PHEA) FOR THE COATING OF GOLD NANOPARTICLES TO BE USED AS ANTIMICROBIAL AGENTS ACTIVATED BY NIR IRRADIATION

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

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…

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

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…

Biomaterials for Biotechnological and Pharmaceutical application

Nuovi Sistemi Polimerici a base di Polisaccaridi/Poliamminoacidici per il Rilascio Colon Specifico Di Farmaci

Evaluation of biodegradability of novel polymeric nanoparticles based on amphiphilic polylactide-polyaspartamide derivatives.

RHEOLOGICAL AND RELEASE PROPERTIES OF FUNCTIONALIZED INULIN HYDROGELS

New amphiphilic copolymers based on a poly(hydroxyethylaspartamide): coating of Au nanostars to obtain antimicrobial photothermal/delivering systems activated by NIR irradiation

NUOVI SISTEMI POLIMERICI A STRUTTURA POLISACCARIDICA/POLIAMMINOACIDICA IMPIEGATI PER IL RILASCIO COLON-SPECIFICO DI ANTICORPI MONOCLONALI

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

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 …

Microfibers obtained by electrospinning of alpha, beta poly(N-2-hydroxyethyl)-DL-aspartamide-g-polylactic acid for potential use in tissue reconstruction

When Functionalization of PLA Surfaces Meets Thiol−Yne Photochemistry: Case Study with Antibacterial PolyaspartamideDerivatives

International audience; In this work we wish to report on the covalent functionalization of polylactide (PLA) surfaces by photoradical thiol–yne to yield antibacterial surfaces. At first, hydrophilic and hydrophobic thiol fluorescent probes are synthesized and used to study and optimize the conditions of ligation on alkyne-PLA surfaces. In a second part, a new antibacterial polyaspartamide copolymer is covalently grafted. The covalent surface modification and the density of surface functionalization are evaluated by SEC and XPS analyses. No degradation of PLA chains is observed, whereas covalent grafting is confirmed by the presence of S2p and N1s signals. Antiadherence and antibiofilm acti…

Inulin-Based Hydrogel for Oral Delivery of Flutamide: Preparation, Characterization, and in vivo Release Studies

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 acti…

NEW IN SITU FORMING HYALURONIC ACID SCAFFOLDS WITH A FIBRILLAR STRUCTURE

Rheological characterization and release properties of inulin-based hydrogels

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…

INULIN-BASED HYDROGELS: RHEOLOGICAL EVALUATION AND IN VITRO DRUG RELEASE STUDIES

Galactosylated micelles for a ribavirin prodrug targeting to hepatocytes.

Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-dl-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver…

Amphiphilic Copolymers Based on Poly[(hydroxyethyl)-d,l-aspartamide]: A Suitable Functional Coating for Biocompatible Gold Nanostars

Novel amphiphilic copolymers have been synthesized based on a biocompatible poly(hydroxyethylaspartamide) (PHEA) backbone, bearing both anchoring groups for gold nanoparticles, such as thiols and disulfide, and conjugable moieties, such as amino groups, the latter as points suitable for appending further functional agents. The strategy was to functionalize α,β-poly[(N-2- hydroxyethyl)-d,l-aspartamide] (PHEA) with PEG2000-NH2 and with ethylenediamine (EDA) obtaining a partially pegylated copolymer with a large number of pendant primary amino groups. A fraction of the latter was conjugated with molecules bearing terminal thiol moieties such as 12-mercaptododecanoic acid (MDA) and disulfide gr…

PREPARAZIONE DI NUOVI SISTEMI POLIMERICI PER IL DRUG DELIVERY

DERIVATI CATIONICI DELL’INULINA OTTENUTI MEDIANTE L’IMPIEGO DELLE MICROONDE PER LA VEICOLAZIONE DI FARMACI A BASE DI ACIDI NUCLEICI

MICROFIBERS OBTAINED BY ELECTROSPINNING OF alpha,beta-POLY(N-2-HYDROXYETHYL)-DL-ASPARTAMIDE-g-POLYLACTID ACID FOR POTENTIAL USE IN TISSUE RECONSTRUCTION

A methacrylic hyaluronic acid derivative for potential application in oral treatment of celiac disease.

Objective: Aim of this work was the synthesis of a methacrylic hyaluronic acid (HA) derivative and the production, via photocrosslinking, of related hydrogels loaded with an endopeptidase intended for a potential oral treatment of celiac disease. Methods: The methacrylic derivative of HA was prepared through a one-pot procedure involving the reaction with ethylenediamine (EDA) and methacrylic anhydride (MA). The obtained derivative, named HA-EDA-MA, was used to prepare photocrosslinked hydrogels loaded with a prolyl endopeptidase derived from Flavobacterium meningosepticum (PEP FM) able to detoxify gliadin. Obtained hydrogels were recovered as gels or freeze-dried powders. Results: Hydrogel…

Inulin vinyl sulfone derivative cross-linked with bis-amino PEG: new materials for biomedical applications

In this work new hydrogels based on biocompatible polymers such as inulin (INU) and O,O'-bis(2-aminoethyl)polyethyleneglycol (PEGBa) have been prepared and charaterized. In particular, INU has been derivatized with divinyl sulfone (DV) thus obtaining the INUDV derivative, a copolymer bearing double bonds highly reactive towards the conjugate addition by nucleophilic molecules. INUDV has been characterized by FT-IR, 1 H-NMR and SEC analyses that have confirmed the success of the derivatization reaction. With the aim to obtain novel hydrogel systems, INUDV derivative has been cross-linked with PEGBa in phosphate buffer solution pH 7.4. The reaction has been carried out for 4 h at room tempera…

Polymeric micelles based on a polyaspartamide copolymer for pulmonary delivery of beclomethasone dipropionate

DEGRADATION STUDIES OF NOVEL POLYMERIC NANOPARTICLES BASED ON AMPHIPHILIC POLYLACTIC ACID-POLYASPARTAMIDE DERIVATIVES