Smart hydrogels with Spheroids of Adipose stem cells for minimally invasive bone and cartilage regeneration

Nanogel-antimiR-31 conjugates affect colon cancer cells behaviour

Soft and flexible nanogels, produced by electron beam (e-beam) irradiation of poly(N-vinyl pyrrolidone) and acrylic acid, were evaluated as delivery devices of the inhibitor of miR-31, a small RNA molecule with an important role in colorectal cancer (CRC) progression. The nanogel carriers developed possess both carboxyl and primary amino groups; the former were activated to react with the primary amino group present in the purposely-functionalised AntimiR-31. Very high conjugation reaction yields were attained, as well as a remarkable colloidal and storage stability of the conjugates. The ability of these nanoconstructs to be internalized by cells and the specific interaction of conjugated …

Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a gl…

Nose-to-brain delivery of insulin enhanced by radiation-engineered nanogels

Recent evidences suggest thet insulin delivery to the brain can be an important pharmacological therapy for some neurodegenerative pathologies, including Alzheimer disease (AD)

On the mechanism of radiation synthesis of nanogels

Radiation-engineered poly(N-vinyl pyrrolidone) nanogels are very interesting biocompatible nanocarriers for i.v. administration of therapeutics and contrast agents for bioimaging among other applications. Nanogels are usually produced upon irradiation of dilute aqueous polymer solutions. Under these conditions, the polymer radicals formed primarily react via intramolecular radical-radical combination forming intramolecular crosslinks. The manufacturing process is fast and effective and grants excellent control of particle size and simultaneous sterilization of the formed nanogels. Interestingly, primary amino groups and carboxyl groups, useful for (bio)conjugation, are also formed in a dose…

Radiation synthesis of nanogels as therapeutic agent vectors

Nanogels (NGs) are physically or chemically crosslinked polymer networks and are promising candidates in the development of therapeutic agent vectors. In fact, thanks to their tunable size and properties, they offer unique advantages, including a large and flexible surface for multivalent bio-conjugation, an internal 3D aqueous environment for incorporation and protection of (bio)molecular drugs, stimuliresponsiveness to achieve temporal and/or site control of the release function and biocompatibility. In order to develop effective NGs-based biomedical devices an inexpensive, robust and versatile synthetic methodology is required. In this perspective, we have produced NGs with high yields a…

Numerical simulations of the kinetics of pulsed electron beam induced synthesis of nanogels in dilute aqueous polymer solutions

Nanogel can be produced by irradiation of dilute aqueous polymer solutions. The nanogels are formed primarily through intramolecular radical-radical crosslinking reactions between two polymer radical sites.

Design, synthesis and characterization of a theranostic nanoplatform for tumor site-specific delivery of doxorubicin

HYDROGELS WITH ORDER POROSITY AT THE MESO-SCALE FOR SENSING

Data concerning the protein absorption and retention properties of xyloglucan-based hydrogel film

In wound dressing applications, exudate absorption and retention are important properties. The data presented here assess the ability of the crosslinked xyloglucan-poly(vinyl alcohol) hydrogel films (XG-PVA), described in "Xyloglucan-based hydrogel films for wound dressing: Structure-property relationships" (Ajovalasit et al., 2018) [1] and "Biocompatibility, hemocompatibility and antimicrobial properties of xyloglucan-based hydrogel film for wound healing application" (Picone et al., 2019), to absorb and retain proteins. These properties were investigated by Comassie blue staining and electrophoresis of Fetal Serum Proteins. (C) 2018 The Authors. Published by Elsevier Inc. This is an open …

Agarose/κ-carrageenan-based hydrogel film enriched with natural plant extracts for the treatment of cutaneous wounds.

Abstract Hydrogels for complex and chronic wound dressings must be conformable, absorb and retain wound exudates and maintain hydration. They can incorporate and release bioactive molecules that can accelerate the healing process. Wound dressings have to be in contact with the wound and epidermis, even for long periods, without causing adverse effects. Hydrogel dressing formulations based on biopolymers derived from terrestrial or marine flora can be relatively inexpensive and well tolerated. In the present article hydrogel films composed by agarose (1.0 wt%), κ-carrageenan at three different concentrations (0.5, 1.0 and 1.5 wt%) and glycerol (3.0 wt%) were prepared without recourse to cros…

On the origin of functionalization in one-pot radiation synthesis of nanogels from aqueous polymer solutions

Radiation-engineered poly(N-vinyl pyrrolidone) nanogels are very interesting biocompatible nanocarriers for i.v. administration of therapeutics and contrast agents for bioimaging. The manufacturing process is fast and effective, it grants excellent control of particle size and simultaneous sterilization of the formed nanogels. Interestingly, primary amino groups and carboxyl groups, useful for (bio)conjugation, are also formed in a dose-dependent fashion. In this paper, by means of both numerical simulations and experiments, the origin of nanogel size control and functionalization is investigated. This understanding offers a new dimension for the design and production of radiation-sculpture…

Two electrochemical methodologies for the synthesis of cyanoacetic acid

Conductive polymer growth onto radiation grafted polyolefines

Conjugation strategies of insulin to nanogels: new hope for nanogels Alzheimer's disease therapy?

Large-scale manufacturing of radiation sculptured therapeutic nanogels

Nanogels (NGs), or small particles formed by physically or chemically crosslinked polymer networks, represent a niche in the development of “smart” nanoparticles for drug delivery and diagnostics. Yet, they offerunique advantages over other systems, including a large and flexible surface for multivalent bio-conjugation; an internal 3D aqueous environment for incorporation and protection of (bio)molecular drugs; the possibility to entrap light-activemolecules, metal or mineral nanoparticles for imaging or phototherapeutic purposes; stimuli-responsiveness to achieve temporal and/or site control of the release function and biocompatibility. The availability of inexpensive, robust and versatile…

Xyloglucan-based hydrogel film for wound dressing: Structure and biological properties relationships

Crosslinked xyloglucan-poly(vinyl alcohol) based hydrogel films have been synthetized and characterized for wound healing applications. Polyvinyl alcohol (PVA) and glycerol (Gro) were added to have an optimal combination of softness, conformability and resilience. Physical hydrogel have been transformed into permanent covalent hydrogels by reaction with glutaraldehyde (GA). Chemical and physical properties of the films have been analyzed by different technique. Moreover, biocompatibility of a selected formulation was assessed in vitro by investigating different aspects, such as cell viability, oxidative stress, mitochondrial dysfunction and specific stress biomarkers. Partial adhesiveness w…

Development and characterization of xyloglucan-poly(vinyl alcohol) hydrogel membrane for Wireless Smart wound dressings

Abstract Hydrogel-based smart wound dressings that combine the traditional favourable properties of hydrogels as skin care materials with sensing functions of relevant biological parameters for the remote monitoring of wound healing are under development. In particular, lightweight, ultra-high frequency radiofrequency identification (UHF RFID) sensor are adjoined to xyloglucan-poly(vinyl alcohol) hydrogel films to battery-less monitor moisture level of the bandage in contact with the skin, as well as wireless transmit the measured data to an off-body reader. This study investigates the swelling behavior of the hydrogels in contact with simulated biological fluids, and the modification of th…

Physico-chemical and mechanical characterization of in-situ forming xyloglucan gels incorporating a growth factor to promote cartilage reconstruction

Abstract The development of growth factors is very promising in the field of tissue regeneration but specifically designed formulations have to be developed in order to enable such new biological entities (NBEs). In particular, the range of therapeutic concentrations is usually very low compared to other active proteins and the confinement in the target site can be of crucial importance. In-situ forming scaffolds are very promising solutions for minimally invasive intervention in cartilage reconstruction and targeting of NBEs. In this work injectable, in-situ forming gels of a temperature responsive partially degalactosylated xyloglucan (Deg-XG) incorporating the growth factor FGF-18 are fo…

RADIATION-ENGINEERED NANOGELS AS GADOLINIUM VECTORS IN BIO-IMAGING

A NEW ROUTE TO OBTAIN PANI-EAA FLEXIBLE FILMS

Xyloglucan-based hydrogel films for the design of "smart" bandages

A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do. Chronic wounds mostly affect people over the age of 60, but a significant proportion is becoming radiation induced chronic wounds caused by cancer radiotherapy. Hydrogels are often used as dressings in the management of a variety of wounds. These materials can help to maintain a moist wound environment, promote natural debridement, hydrate necrotic tissue, absorb slough and exudates.We are developing hydrogel dressings that can enable constant monitoring of selected key parameters through embedded radio-sensors, providing information on the progress of the re…

Radiation engineered functionalized nanogels as platform for biomedical nanocarriers

Insulin Nanogels: a New Strategy for the Treatment of Alzheimer’s Disease

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signaling are involved in brain cognitive functions and their dysfunction is implicated in Alzheimer’s disease (AD) degeneration. Thus, administration of insulin could be a strategy for AD treatment. For this aim we have designed, synthesized and characterized a nanogel system (NG) to deliver insulin to the brain, as a tool for the development of a new therapy for AD. A carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system produced by ionizing radiation was chosen as substrate for the covalent attachment of insulin or fluorescent molecules relevant for its characterization. Biocompatibility of the naked c…

Radiation-tailored xyloglucan-doxorubicin nanoparticles for cancer therapy

Polysaccharides are long chains of monosaccharides linked by glycosidic bonds. They are widely utilized in biomedical applications, for tissue engineering and wound management, and as excipients of pharmaceutical formulations. In cancer therapy, the development of nanoscale drug delivery systems aims at addressing issues related to the low efficacy of chemotherapeutics and protein drugs due to poor solubility and stability, and to off-target effects that severely affect patients’ body conditions. Biocompatibility, availability of functional groups, amenability of chemical derivatisation and multifunctional conjugation with drugs and targeting ligands make polysaccharide nanoparticles intere…

Inherently fluorescent polyaniline nanoparticles in a dynamic landscape

Abstract In this paper we report for the first time on the emissive behavior of two polyaniline (PANI) nanoparticle systems produced via oxidative chemical polymerization in the presence of either poly(vinyl alcohol) (PVA) or chitosan as polymeric stabilizers in water. The emission from PANI nanoparticles is irreversibly quenched by an increase of pH of the suspending medium from acid to neutral (chitosan–PANI) or alkaline (PVA–PANI). Conversely, PANI nanorods synthesized in the same conditions of the above, but in presence of poly(N-vinyl pyrrolidone), is not emissive at any pH. The role of the polymeric surfactant as a soft template is key in controlling the morphology and the properties …

Radiation engineered nanogels as platform for next-generation of medical diagnostics and therapeutics

Minimalism in radiation synthesis of biomedical functional nanogels.

A scalable, single-step, synthetic approach for the manufacture of biocompatible, functionalized micro- and nanogels is presented. In particular, poly(N-vinyl pyrrolidone)-grafted-(aminopropyl)methacrylamide microgels and nanogels were generated through e-beam irradiation of PVP aqueous solutions in the presence of a primary amino-group-carrying monomer. Particles with different hydrodynamic diameters and surface charge densities were obtained at the variance of the irradiation conditions. Chemical structure was investigated by different spectroscopic techniques. Fluorescent variants were generated through fluorescein isothiocyanate attachment to the primary amino groups grafted to PVP, to …

ENGINEERED NANOGELS FOR BIOLOGICAL DRUGS TRANSPORT

Nowadays the nanocarrier strategy, aimed to rebuild the tumor therapy approach in a winning way, is growing very fast. This is in the direction to engender nanocarriers having synergistic action by the “biological drugs” transported, the capability to recognize specific targets and the molecular architecture that allows them to perform at the best their therapeutic functions. We are building engineered nanocarriers having different functions (control cell cycle, induce apoptosis, etc.) as well as the capability to recognize specific targets (tumor cells, angiogenic and/or sprouting endothelial cells); moreover, they must have also the ability to escape the host immunosystem, such that not t…

Crosslinking of polymers activated by electrogenerated hydroxyl radicals.

Nanogels (NGs) are systems created by crosslinking of polymers taking nanosized dimensions and they have been proposed for biomedical and pharmaceutical applications due to their soft consistency, biocompatibility and good chemical properties that make them excellent drug delivery agents (1). Differently from typical hydrogels, nanogels are able to dissolve in solvents and to swell releasing the drug molecules loaded in the nano-vector. Furthermore, if properly functionalized with reactive groups, these materials can represent a very interestingly vector for different pharmacological treatments (2). Several methods have been investigated to prepare polymeric nanogels starting from preformed…

Comparative studies of the Pschorr reaction in the pyrazole series. Access to the new dibenzo[e,g]pyrazolo[1,5-a][1,3]diazocine system of pharmaceutical interest

The diazonium tetrafluoroborate 11 obtained from 2-amino-N-methyl-N-(1-phenyl-3- methylpyrazol-5-yl)benzamide was transformed in dry acetonitrile via an ionic or radical pathway. Differences were observed with respect to ionic or radical transformations in aqueous media of the analogous diazonium hydrogen sulfate 1 derived from the same amine. In acetonitrile solution, the ionic pathway was characterized by an increased yield of 1,4-dimethyl- 3-phenyl-pyrazolo(3,4-c)isoquinolin-5-one 4 and by the formation of its isomer, the new derivative 7,9-dimethyldibenzo(e,g)pyrazolo(1,5-a)(1,3)diazocin-10(9H)-one 12. When the reaction followed a radical pathway, the pyrazolo(3,4-c)isoquinoline derivat…

Ethanol vapor optical sensors based on polystyrene opals infiltrated with hydrogel

Recombinant mussel protein Pvfp5β enhances cell adhesion of poly(vinyl alcohol)/k-carrageenan hydrogel scaffolds

Polymeric hydrogels are increasingly being considered as a scaffold for tissue engineering because they show similarity to the extracellular matrix (ECM) of many tissues. To control various cellular processes, hydrogels are often functionalized or loaded with various bioactive molecules such as: specific ligands for adhesion receptors, growth factors, hormones, enzymes, and other natural or synthetic regulators of cellular behavior [1]. Cell adhesion is essential for cell communication and regulation of the cell cycle and is therefore of vital importance in tissue engineering. Biomimetic approaches have been investigated to facilitate cell-scaffold adhesion interactions. In particular, the …

Electrochemical oxidation of tetramethoxy precursor as a key step for the synthesis of coenzyme Q10

The feasibility of electrosynthesis of coenzyme Q10 (1) by electrooxidation of tetramethoxy precursor (2) has been investigated at carbon, Pt and BDD anodes in a divided cell. The process strongly depends on the applied potential, anode material and water content of the solvent. At carbon anodes in CH3CN/CH2Cl2 + 0.15 M Bu4NBF4 at proper operative conditions high faradic efficiency (>60%) and excellent selectivity (95–97%) of the target product were obtained. Keywords: Electrosynthesis, Coenzyme Q10, Anodic oxidation

Nose-to-brain delivery of insulin enhanced by a nanogel carrier.

Recent evidences suggest that insulin delivery to the brain can be an important pharmacological therapy for some neurodegenerative pathologies, including Alzheimer disease (AD). Due to the presence of the Blood Brain Barrier, a suitable carrier and an appropriate route of administration are required to increase the efficacy and safety of the treatment. Here, poly(N-vinyl pyrrolidone)-based nanogels (NG), synthetized by e-beam irradiation, alone and with covalently attached insulin (NG-In) were characterized for biocompatibility and brain delivery features in a mouse model. Preliminarily, the biodistribution of the "empty" nanocarrier after intraperitoneal (i.p.) injection was investigated b…

SELF-ASSEMBLY OF DEGALACTOSYLATED XYLOGLUCAN FROM TAMARIND SEEDS

The role of molecular oxygen in the formation of radiation-engineered multifunctional nanogels

Abstract Nanogels are very promising biomedical nanodevices. The classic “radiation chemistry-based” approach to synthetize nanogels consists in the irradiation with pulsed electron beams of dilute, N2O-saturated, aqueous solutions of water-soluble polymers of the “crosslinking type”. Nanogels with controlled size and properties are produced in a single irradiation step with no recourse to initiators, organic solvents and surfactants. This paper combines experimental syntheses, performed with two e-beam irradiation setups and dose-ranges, starting from poly(N-vinyl pyrrolidone) solutions of various concentrations, both in N2O-saturated and air-saturated initial conditions, with the numerica…

Pharmaceutical compositions in the form of gel containing xyloglucan and alcohols for the controlled release of active ingredients

The invention relates to gel compositions comprising pharmaceutical active ingredients. The composition comprises xyloglucan at concentration between 0.1% and 10.0% by total weight of the composition, together with a primary alcohol at a concentration between 20.0 and 50.0% by total weight of the composition. The invention also describes a process for the preparation of the composition and its use in the treatment of pathologies wherein a controlled release of the active principle is useful.

Multifunctional nanogels from e-beam irradiation of PVP aqueous solutions, only

Nanogels (NGs) are 3D networks of crosslinked hydrophilic polymers with nanoscalar dimensions. Due to their structure and physico-chemical properties, they are a promising nanomaterial platform for site-specific drug delivery and diagnostic nanodevices.

Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability.

Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increa…

Radiation curing of carbon fibre composites

Epoxy/carbon fibre reinforced composites were produced by means of e-beam irradiation through a pulsed 10 MeV electron beam accelerator. The matrix consisted of a difunctional epoxy monomer (DGEBA) and an initiator of cationic polymerisation, while the reinforcement was a unidirectional high modulus carbon fibre fabric. Dynamic mechanical thermal analysis was carried out in order to determine the cross-linking degree. The analysis pointed out a nonuniformity in the cross-linking degree of the e-beam cured panels, with the formation of clusters at low Tg (glass transition temperature) and clusters at high Tg. An out-of-mould post irradiation thermal treatment on e-beam cured samples provides…

E-beam crosslinked, biocompatible functional hydrogels incorporating polyaniline nanoparticles

Abstract PANI aqueous nanocolloids in their acid-doped, inherently conductive form were synthesised by means of suitable water soluble polymers used as stabilisers. In particular, poly(vinyl alcohol) (PVA) or chitosan (CT) was used to stabilise PANI nanoparticles, thus preventing PANI precipitation during synthesis and upon storage. Subsequently, e-beam irradiation of the PANI dispersions has been performed with a 12 MeV Linac accelerator. PVA-PANI nanocolloid has been transformed into a PVA-PANI hydrogel nanocomposite by radiation induced crosslinking of PVA. CT-PANI nanoparticles dispersion, in turn, was added to PVA to obtain wall-to-wall gels, as chitosan mainly undergoes chain scission…

Gadolinium-chelating nanogels as MR contrast agesnts specifically targeting tumor cells

Development of multifunctional nanogels coordinating paramagnetic ions and displacing targeting ligands for preferential accumulation into tumors. Low molecular-weight Gd-chelates are widely used in clinical MRI for various purposes. However, these contrast agents (CAs) have several shortcomings: they rapidly extravasate from blood vessels to the interstitial space, have a short circulation times and show poor contrast at high magnetic fields. Incorporating gadolinium into flexible nanogels has the potential of increasing intravascular half-life, accumulation and retention in specific body compartments of the CA as well as increasing the MR signal, since many metal ions can be coordinated t…

Synthesis od epoxy/carbon fiber composites induced by e-beam. Study of the effect of hydrothermal ageing on thermal and mechanical properties

NANOGELS AS USEFUL TOOL FOR ALZHEIMER’S DISEASE THERAPY

Electrochemical reduction of macrocyclic polysulfonamides for the synthesis of polyazamacrocycles

Maltose-conjugated chitosans induce macroscopic gelation of pectin solutions at neutral pH

Injectable polymer scaffolds are particularly attractive for guided tissue growth and drug/cell delivery with minimally invasive intervention. In the present work, "all-polymeric" gelling systems based on pectins and water-soluble maltose-conjugated chitosans (CM) have been developed. Maltose-conjugated chitosan has been synthesized at three different molar ratios, as evaluated by FITR analysis and fluorimetric titration. A thorough rheological characterization of the blends and their parent solutions has been performed. Macroscopic gelation has been achieved by mixing the high esterification degree pectins with CM at higher maltose grafted to chitosan contents. Gels form in a few minutes a…

Structure and biological evaluation of amino-functionalized PVP nanogels for fast cellular internalization

Abstract Aminopropyl methacrylamide chloride-graft-poly(N-vinyl pyrrolidone) nanogels (NGs) were designed to exploit the favorable properties of poly(N-vinyl pyrrolidone) (PVP), such as its high affinity to water and complexation ability of ions, molecules and macromolecules, with the availability of primary amino groups for bioconjugation reactions. A thorough structural characterization of the nanoscalar networks was performed via 1 H NMR and solid state 13 C NMR spectroscopies, while solid state NMR relaxation time measurements completed the NGs description in terms of polymer network density. Information on the hydrodynamic size and surface charge densities were sought via dynamic light…

Un unexpected ring carboxylation in the electrocarboxylation of substituted aromatic ketones

Radiation sculpured nanogels as platform for novel therapeutic systems

Multifunctional and Bio-hybrid Hydrogel As bioartificial Matrices and Drug Delivery Devices

Methodological approach for evaluating the geo-exchange potential: VIGOR Project

In the framework of VIGOR Project, a national project coordinated by the Institute of Geosciences and Earth Resources (CNR-IGG) and sponsored by the Ministry of Economic Development (MiSE), dedicated to the evaluation of geothermal potential in the regions of the Convergence Objective in Italy (Puglia, Calabria, Campania and Sicily), is expected to evaluate the ability of the territory to heat exchange with the ground for air conditioning of buildings. To identify the conditions for the development of low enthalpy geothermal systems collected and organized on a regional scale geological and stratigraphic data useful for the preparation of a specific thematic mapping, able to represent in a …

CONJUGATION STRATEGIES OF INSULIN TO NANOGELS AND BIOLOGICAL ACTIVITY TESTS

Influence of gamma-irradiation on thermally-induced mesoscopic gelation of degalactosylated xyloglucans

Thermoresponsive degalactosylated xyloglucans have been already proposed as in situ gelling scaffolds for tissue engineering, due to their reversible macroscopic thermal gelation at body temperature and biodegradability. The highly branched, hydroxyl group-rich molecular structure renders xyloglucans interesting raw materials also in the form of micro/nanoparticles for application as nanoscalar drug delivery devices in cosmetic and pharmaceutical formulations. Owing to their natural source, xyloglucans show high average molecular weight, broad molecular weight distribution and poor water solubility, as large and compact aggregates usually form via inter-molecular hydrogen bonding. Co-60 gam…

Water-borne polymeric nanoparticles for glutathione-mediated intracellular delivery of anticancer drugs

A new family of water-borne, biocompatible and carboxyl- functionalized nanogels was developed for glutathione- mediated delivery of anticancer drugs. Poly(N-vinyl- pyrrolidone)-co-acrylic acid nanogels were generated by e- beam irradiation of aqueous solutions of a crosslinkable polymer, using industrial-type linear accelerators and set- ups. Nanogels physico-chemical properties and colloidal stability, in a wide pH range, were investigated. In vitro cell studies proved that the nanogels are fully biocompatible and able to quantitatively bypass cellular membrane. An anticancer drug, doxorubicin (DOX), was linked to the carboxyl groups of NGs through a spacer containing a disulphide cleavab…

Water-borne e-beam crosslinked nanogels as nanomaterials platform for drug delivery

RADIATION CURING OF CARBON FIBRE COMPOSITES

Degalatosylated xyloglucan hydrogels: influence of irradiation conditions on physico-chemical properties and structure

Ionizing radiation-engineered nanogels as insulin nanocarriers for the development of a new strategy for the treatment of Alzheimer's disease

A growing body of evidence shows the protective role of insulin in Alzheimer's disease (AD). A nanogel system (NG) to deliver insulin to the brain, as a tool for the development of a new therapy for Alzheimer's Disease (AD), is designed and synthetized. A carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system produced by ionizing radiation is chosen as substrate for the covalent attachment of insulin or fluorescent molecules relevant for its characterization. Biocompatibility and hemocompatibility of the naked carrier is demonstrated. The insulin conjugated to the NG (NG-In) is protected by protease degradation and able to bind to insulin receptor (IR), as demonstrated by immunofl…

Synthesys of coenzymes Qn by electrochemical oxidation of tetramethoxy precursor

Electrochemical detosylation of macrocyclic polysulfonamides for the synthesis of cyclen

Dielectric characterization of biocompatible hydrogels for application to Epidermal RFID devices

Functionalized skin-like membranes are currently under investigation for the design of a new class of Epidermal Electronics devices for sensing and healing applications. The dynamic response of epidermal antennas in presence of absorption and release of fluids is a key-point to design RFID radio-sensors and actuators. This paper addresses the characterization of the dielectric property of PVA-based biocompatible hydrogel membranes in the UHF RFID band by means of a modified ring resonator. Samples having different compositions are measured in the dry state as well as when exposed to a progressive release of body fluids emulating perspirations or wound exudates. It was found that the permitt…

Opals infiltrated with a stimuli-responsive hydrogel for ethanol vapor sensing

We report on a novel class of optical materials for ethanol vapor sensing, based on polystyrene opals infiltrated with an innovative stimuli responsive hydrogel. We describe the fabrication process of the bare polystyrene opals and their subsequent infiltration. The optical characterization of the photonic crystal templates was performed to prove the good quality of the samples. Measurements on the infiltrated opals showed that the transmission spectra in the visible range strongly change at varying concentrations of ethanol vapor. The fabricated structures show a linear optical response in the visible range, for high values of ethanol concentration.

FOLATE-DECORATED E-BEAM CROSSLINKED NANOGELS TO ENHANCE UPTAKE BY TUMOR CELLS

E-Beam Crosslinked Polymeric and Bio-Hybrid Nanocarriers for Drug Delivery and Bioimaging

Control of end-of-life oxygen-containing groups accumulation in biopolyesters through introduction of crosslinked polysaccharide particles

The formulation of bio-based materials with good performance in service and controlled end-of-life is imperative for an effective circular economy. In this work, an innovative approach to induce and control the end-of-life of biodegradable polyesters through introduction of crosslinked polysaccharide particles is proposed. Chitosan (Ch) has been subjected to ionotropically crosslinking and then added to polylactic acid (PLA) at different amounts (1.0–4.0%w) by melt mixing. All obtained results suggest that the addition of crosslinked Ch (cCh) particles does not modify significantly the investigated biopolyester properties. Specifically, the thermal analysis of the composites reveals that th…

Macromolecular engineering of hydrogels: from macro to nano scalar materials for different levels of biointeraction

Hydrogel films engineered in a mesoscopically ordered structure and responsive to ethanol vapors

Abstract Responsive hydrogels filling the interstitial spaces of photonic crystals can form mesoscopically structured materials, which exhibit reversible shifts in the Bragg diffracted light as a response of environmental changes. These materials can be used to generate chemical or biochemical sensors. The present work reports on the synthesis and characterization of ethanol responsive hydrogels that can be used in the design of novel breathalyzers. The dynamic mechanical behavior of the macroscopic hydrogels and their swelling features in the presence of different liquids or vapors have been investigated to orientate the choice of the best responsive material and curing process. The swelli…

Recombinant mussel protein Pvfp5β enhances cell adhesion of poly(vinyl alcohol)/k-carrageenan hydrogel scaffolds

Polymeric hydrogels are increasingly considered as scaffolds for tissue engineering due to their extraordinary resemblance with the extracellular matrix (ECM) of many tissues. As cell adhesion is a key factor in regulating important cell functions, hydrogel scaffolds are often functionalized or loaded with a variety of bioactive molecules that can promote adhesion. Interesting biomimetic approaches exploit the properties of mussel-inspired recombinant adhesive proteins. In this work, we prepared hydrogel scaffolds with a 50%w mixture of k-carrageenan (kC) and polyvinyl alcohol (PVA), by a two-step physical gelation process, and we coated them with Perna viridis foot protein-5 beta (Pvfp5 be…

Radiation engineered polymer nanocarriers for a new generation of nanoparticles based tumor specific radiopharmaceuticals

High energy radiation processing for the synthesis of insulin nanocarriers for the development of a new strategy for the treatment of Alzheimer's Disease

Nanogels are nanoscalar polymeric networks, characterized by a dynamic internal structure and a flexible adaptive shape. When they are used as drug carriers, their flexibility and shape changing ability can facilitate the bypass of biological barriers, ensure protection of the payload and enable interaction of any attached ligand with its receptors. Poly(N-vinyl pyrrolidone)-co-acrylic acid nanogels (NGs) have been produced by ebeam irradiation of diluted aqueous solutions of a water-soluble polymer in the presence of a small amount of acrylic acid. In particular, industrial accelerators and the typical set-ups and doses applied for sterilization have been used. [1, 2] Particle size, molecu…

Temperature-responsive cellulose-based hydrogels as draw agents in Forward Osmosis

Forward Osmosis is a powerful tool to produce clean water at a low cost if appropriate draw agents and regeneration methods are employed (1). In this frame, stimuli-responsive hydrogels are interesting candidates due to their ability to uptake water and release it under physical stimuli, such as hydrostatic pressure and temperature variations. In particular, temperature-responsive hydrogels that are able to absorb large amount of water at room temperature and release it upon a slight temperature increase are very appealing candidates because they can be regenerated easily and with very low energy consumption (2). Chemical stability and biocompatibility are two further requirements that hydr…

High-energy radiation processing, a smart approach to obtain PVP-graft-AA nanogels

Abstract Poly(N-vinylpyrrolidone)-grafted-acrylic acid biocompatible nanogels (NGs) were prepared using an exiting industrial-type electron accelerator and setups, starting from semi-dilute aqueous solutions of a commercial PVP and the acrylic acid monomer. As a result, NGs with tunable size and structure can be obtained quantitatively. Sterility was also imparted at the integrated dose absorbed. The chemical structure of the NGs produced was confirmed through Fourier Transformer Infrared Spectroscopy (FT-IR). The molecular and physico-chemical properties of NGs, such as the hydrodynamic dimensions and surface charge densities, for various polymer and monomer concentrations in the irradiate…

Gelation of degalactosylated xyloglucan from nano to macroscopic scale

Partially degalactosylated xyloglucans are able to form thermo-reversible gels in aqueous solution at physiological temperature. This property makes them very promising materials for tissue engineering. Moreover, due to a highly branched, hydroxyl group-rich molecular structure, xyloglucans are particularly interesting for manufacturing of micro/nanoparticles to be used as nano-scalar delivery devices of active ingredients in cosmetic and pharmaceutical formulations. Here we present results on the temperature-induced self-assembly of degalactosylated xyloglucan at varying polymer concentration from dilute to semi-dilute regime. Our aim is to investigate the gelation mechanism for gaining in…

Electrochemical synthesis of coenzymes Qn by oxidation of tetramethoxy precursors

The electrochemical oxidation of tetramethoxy precursors (2) to coenzymes Q (n) (1) at a carbon anode was investigated both in a bench-scale batch electrochemical reactor and in a continuous recirculation reaction system equipped with a parallel-plate electrochemical divided cell. High faradic efficiency (> 60%) and excellent selectivity (> 90%) in coenzymes Q (n) were obtained in CH3CN or CH3CN/CH2Cl2 + 0.15 M Bu4NBF4 under potentiostatic or amperostatic alimentation.

Large-scale radiation manufacturing of hierarchically assembled nanogels

Nanogels (NGs), or small particles formed by physically or chemically crosslinked polymer networks, represent a niche in the development of "smart" nanoparticles for drug delivery and diagnostics. They offer unique advantages over other systems, including a large and flexible surface for multivalent bio-conjugation; an internal 3D aqueous environment for incorporation and protection of (bio)molecular drugs; the possibility to entrap active metal or mineral cores for imaging or phototherapeutic purposes; stimuli-responsiveness to achieve temporal and/or site control of the release function and biocompatibility. The availability of inexpensive and robust preparation methodologies is at the ba…

Optical sensors for ethanol vapor based on polystyrene opals infiltrated with hydrogel

This paper deals with a novel class of optical sensors for ethanol vapor, based on polystyrene opals infiltrated with a hydrogel sensitive to ethanol. Optical characterization of such opals has been performed, proving their effectiveness as sensors

POLYSACCHARIDE-BASED HYDROGELS FOR MYOCARDIUM REMODELING

Idrogeli a base di xyloglucano per la produzione di medicazioni avanzate nel trattamento delle ferite

In questo lavoro sono stati preparati film sottili di idrogelo (reticolati fisicamente o chimicamente) a base di xyloglucano (XG) e XG/polivinilalcol (PVA), a cui si è aggiunto glicerolo come plasticizzante. Lo xyloglucano è un polisaccaride di origine vegetale, caratterizzato da una catena principale di (1,4)--Dglucosio con ramificazioni laterali di (1-6)-α-xilosio, parzialmente sostituite con (1-2)–β galattosio. E’ stata indagata la possibilità di modulare la densità di reticolazione dell’idrogelo per ottenere il miglior compromesso tra resistenza meccanica e flessibilità, l’integrità strutturale nel tempo e la capacità di assorbire fluidi biologici o trattenere l’umidità. Inoltre, ne è …

Neuroprotective effect of a new Insulin-Nanogel system

Nanogels (NGs) have a great potential in the development of “smart” nanocarriers for (bio)molecular drugs and contrast agent for bioimaging. They are formed by physically or chemically crosslinked polymer networks, characterized by a large and flexible surface available for multivalent bioconjugations. NGs can be produced with high yields and through-puts by pulsed electron-beam irradiation of dilute aqueous solutions of water-soluble biocompatible polymers. In this work, a carboxyl functionalized nanogel system (NG), generated by pulsed e-beam irradiation of a semi-dilute poly(N-vinyl pyrrolidone) (PVP) aqueous solution in the presence of acrylic acid, with an average diameter in the 60-70…

Oligonucleotide-decorated carboxyl-modified PVP nanogels: a new platform for diagnosis and gene-therapy.

Nanogels, or nanoscalar chemically crosslinked polymer networks, were generated by simultaneous crosslinking of Poly(N-vinyl pyrrolidone) (PVP) and grafting of acrylic acid (AA) monomer through e-beam irradiation of their aqueous solutions. The yield of the process is very high and no separation or complex purification procedures are required since no recourse to surfactants or organic solvents is made. The administered irradiation dose (40 kGy) imparts also sterility to the obtained nanogels in the form of aqueous dispersions. Control of particle size and size-distribution can be achieved by proper selection of the irradiation conditions. In particular, we obtained nanogel variants with av…

Electrocarboxylation of aromatic ketones: Influence of operative parameters on the competition between ketyl and ring carboxylation

Abstract The purpose of this work is to investigate the effect of operational parameters on the competition between the formation of the target 2-hydroxy-2-arylpropanoic acid and ring carboxylation in the electrocarboxylation of aromatic ketones. For the investigated ketones, this competition has been found to be dramatically influenced by different parameters such as the water content and the ratio between the carbon dioxide and the ketone concentrations (q = [CO2]/[ketone]). In particular, the target carboxylic acid formation can be favoured with respect to ring carboxylation by operating at high q ratios or by addition of small amounts of H2O to the reaction medium. An increase of the wa…

New insights on the mechanism of PVP nanogels radiation synthesis

In this work, the H2O2 build-up for several system compositions and irradiation conditions was investigated, by using the Ghormley triiodide method. Interestingly, the application of the method has revealed the occurrence of two concurrent reactions, the expected one responsible for the I3 - production (by reaction with the H2O2 formed upon irradiation) and one that is responsible for I3 - consumption. Both the concentrations of I3 - -forming and I3 - -consuming species are dose-dependent and polymer concentration-dependent. The kinetic study of the two reactions and some further experiments carried out with model molecules will be described. We believe that the results of this study can of…

Radiation-engineered multifunctional nanogels: a versatile platform with theranostic capabilities for cancer

Under a rational desing, combining biologically active molecules, ligand to specific cell receptors and fluorescent, radioactive or paramagnetic labels into a single nano-object can bride the unique properties of the individual components and impruve conventional sensing, imaging and therapeutic efficaces.

Temperature-induced self-assembly of degalactosylated xyloglucan at low concentration

Xyloglucan is a natural polysaccharide having a cellulose-like backbone and hydroxyl groups-rich side-chains. In its native form the polymer is water-soluble and forms gel only in presence of selected co-solutes. When a given fraction of galactosyl residues are removed by enzymatic reaction, the polymer acquires the ability to form a gel in aqueous solution at physiological temperatures, a property of great interest for biomedical/pharmaceutical applications. This work presents data on the effect of a temperature increase on degalactosylated xyloglucan dispersed in water at concentration low enough not to run into macroscopic gelation. Results obtained over a wide interval of length scales …

Radiation Engineering of Xyloglucan Hydrogels

Xyloglucans (XGs) are interesting substrates for the production of scaffolds for tissue engineering, drug delivery depots and hydrogel dressings, thanks to their ability to gel in appropriate conditions, such as in the presence of hydro-alcoholic solvents or by addition of sugar molecules. Due to their natural source, they are characterized by high average molecular weights and broad molecular weight distributions. High energy irradiation is a suitable tool to reduce polysaccharides molecular weight without a dramatic alteration of the polymer chemical structure and gelation ability. In this work, the effect of the radiation dose on the molecular weight of a XG derived from Tamarind seeds i…

Insulin Nanogel as New Strategy for the Treatment of Alzheimer’s Disease

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signaling are involved in brain cognitive functions and their dysfunction is implicated in neuronal degeneration associated with Alzheimer's disease (AD). Thus, the administration of insulin to the brain could be a strategy for the prevention and treatment of AD disease. With this aim, we have designed, synthesized and characterized a nanogel system (NG) that can be used as substrate for the conjugation of insulin and/or fluorescent molecules relevant for their characterization. In particular, a carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system, has been produced by ionizing radiation starting from th…

Periodically nanostructured hydrogels for ethanol vapors sensing

Chemical sensing using optics has been under extensive research all over the world during last decades and many optical chemical sensors are nowadays finding increasing applications in industry, environmental monitoring, medicine, biomedicine and chemical analysis. These optical sensors can be based on various optical principles, such as absorbance, reflectance or transmittance, luminescence and fluorescence, covering different regions of the spectrum (UV, visible, IR, NIR). Optical chemical sensors have several advantages over conventional electricity-based sensors, in terms of selectivity, immunity to electromagnetic interference, higher sensitivity, and they are also relatively inexpensi…

Biocompatibility, hemocompatibility and antimicrobial properties of xyloglucan-based hydrogel film for wound healing application.

Crosslinked xyloglucan-poly(vinyl alcohol) based hydrogel films are interesting materials for wound healing applications. This work focuses on the hydrolytic degradation and consequent morphological modification of a XG-PVA film and on its interaction with cells, blood, bacteria. Biocompatibility of the film was assessed in vitro by investigating different aspects, such as cell viability, oxidative stress level, mitochondrial dysfunction and specific stress biomarkers. Partial adhesiveness was demonstrated by performing different attaching assays and phalloidin staining. Hemocompatibility of XG-PVA film after interaction with blood was evaluated by using a multi-parametric approach, includi…

κ-Carrageenan and PVA blends as bioinks to 3D print scaffolds for cartilage reconstruction.

3D printing of polymeric scaffolds and autologous stem cells is a promising tool for damaged facial cartilage reconstruction surgeries. To this end, suitable bioinks are needed to generate scaffolds with the required morphological and functional features. We formulated hydrogel bioinks using k-Carrageen (kC) and poly(vinyl alcohol) (PVA) in three different weight ratios. The kC gives the systems the ability to undergo rapid sol-to-gel transitions upon cooling from 60 °C and above to body temperature, while the PVA is used as rheology modifier and porogen. The latter is crosslinked after molding or printing by freeze-thaw cycling for 1 day (FT1) or 5 days (FT5). To select the most suitable f…

Large-scale Radiation Manufacturing of Hierarchically Assembled Nanogels

Nanogels (NGs), or small particles formed by physically or chemically crosslinked polymer networks, represent a niche in the development of “smart” nanoparticles for drug delivery and diagnostics. They offer unique advantages over other systems, including a large and flexible surface for multivalent bio-conjugation; an internal 3D aqueous environment for incorporation and protection of (bio)molecular drugs; the possibility to entrap active metal or mineral cores for imaging or phototherapeutic purposes; stimuli-responsiveness to achieve temporal and/or site control of the release function and biocompatibility. The availability of inexpensive and robust preparation methodologies is at the ba…

Macromolecular design and preparation of nanogels as pharmaceutical carriers

Synthesis of polymer nanogels by electro-Fenton process: investigation of the effect of main operation parameters

Recently, electro-Fenton (EF) process has been shown as a promising, facile, effective, low cost and environmentally-friendly alternative for synthesizing polymer nanogels suitable as biocompatible nanocarriers for emerging biomedical applications. Here, the electrochemically-assisted modification of poly(vinylpyrrolidone) (PVP) by EF process was studied to assess the role of key operation parameters for a precise modulation of polymer crosslinking and its functionalization with [sbnd]COOH and succinimide groups. The dimensions of the nanogels, in terms of hydrodynamic radius (Rh) and weight-average molecular weight (Mw), can be tuned up by controlling the electrolysis time, current density…

UN NUOVO METODO PER OTTENERE FILM FLESSIBILI EAA-PANI

TEMPERATURE-TRIGGERED MACROSCOPIC GELATION OF IRRADIATED XYLOGLUCANS FOR BIOMEDICAL APPLICATIONS

Optical characterization of polystyrene direct opals and of inverse-opal hydrogels

Gadolinium-chelating nanogels as MR contrast agents specifically targeting tumor cells

Aims and objectives Methods and materials Results Conclusion Personal information References

In-situ gelling xyloglucan formulations as 3D artificial niche for adipose stem cell spheroids.

Abstract Three-dimensional spheroidal cell aggregates of adipose stem cells (SASCs) are a distinct upstream population of stem cells present in adipose tissue, with enhanced regeneration properties in vivo. The preservation of the 3D structure of the cells, from extraction to administration, can be a promising strategy to ensure optimal conditions for cell viability and maintenance of stemness potential. With this aim, an artificial niche was created by incorporating the spheroids into an injectable, in-situ gelling solution of partially degalactosylated xyloglucan (dXG) and an ad hoc formulated culture medium for the preservation of stem cell spheroid features. The evolution of the mechani…

Analysis of Hydrological and Landslide Hazards at Castellammare Del Golfo (Northern Sicily)

Catastrophic floods or mass movements occur all too often owing to small streams overflowing their banks or to slope instabilities whose evolution has a more or less tragic impact on people and property; these events are the consequence of a poor understanding of the dynamics of geomorphological processes and of the laws governing them. This paper is focused on the case study of Castellammare del Golfo, a town in the province of Trapani. The study analysed the geological risk due to the geomorphology of the area and to the urban sprawl that it has experienced in the past decades. Geomorphological processes have a strategic role to play in spatial planning and management instruments and in t…

Functional consequences of prey acclimation to ocean acidification for the prey and its predator

Ocean acidification is the suite of chemical changes to the carbonate system of seawater as a consequence of anthropogenic carbon dioxide (CO2) emissions. Despite a growing body of evidences demonstrating the negative effects of ocean acidification on marine species, the consequences at the ecosystem level are still unclear. One factor limiting our ability to upscale from species to ecosystem is the poor mechanistic understanding of the functional consequences of the observed effects on organisms. This is particularly true in the context of species interactions. The aim of this work was to investigate the functional consequence of the exposure of a prey (the mussel Brachidontes pharaonis) t…

Facile crosslinking of poly(vinylpyrrolidone) by electro-oxidation with IrO2-based anode under potentiostatic conditions

Abstract: The modification of polymer architectures by reaction with chemically adsorbed hydroxyl radicals has been thoroughly investigated by electrolyzing dilute aqueous solutions of the biocompatible polymer poly(vinylpyrrolidone) (PVP), using an undivided electrolytic cell with a Ti/IrO2–Ta2O5(DSA®) anode. Several electrolyses were performed to assess the influence of the applied potential, the circulated charge and the PVP concentration, which was always kept low to avoid chain overlapping. From the results obtained, it can be concluded that the electro-oxidation of PVP solutions using a cheap anode is an effective method to crosslink initially isolated polymer chains, eventually incre…

Direct electrochemical detosylation of tetratosylcyclen to cyclen with carbon cathodes

The electrochemical detosylation of tetratosylcyclen to cyclen (1,4,7,10-tetraazacyclododecane) in aprotic solvents at a carbon cathode was investigated both in a bench-scale batch electrochemical reactor and in a continuous batch recirculation reaction system equipped with a parallel-plate electrochemical cell. Yields and faradaic efficiency in cyclen, respectively, of 80 and 55% were obtained in the bench-scale reactor working in acetonitrile. It was found that the faradaic efficiency in cyclen depends on the competition between the reduction of the tetratosylcyclen and parasitic processes as the reduction of the tetraalkylammonium cations present in the supporting electrolyte. We have ob…

Synthetic and natural polymer nanoparticles as bio-imaging and therapeutic agent vectors

An unexpected ring carboxylation in the electrocarboxylation of aromatic ketones

The electrocarboxylation of various aromatic ketones, carried out in N-methyl-2-pyrrolidone (NMP) in a diaphragmless cell equipped with a carbon cathode and an aluminium sacrificial anode, yielded, among the products, the target hydroxy acids, the corresponding alcohols and pinacols and, quite surprisingly, detectable amounts of substituted benzoic acids and cycloexene carboxylic acids. These compounds arise from a never reported before electrocarboxylation on the aromatic ring, respectively, for substitution of an aromatic hydrogen and from an addition reaction. For example, the electrocarboxylation of acetophenone gave rise to the substituted benzoic acids in ortho, para and meta position…

High-energy radiation process, a "facile" and "versatile" approach to obtain PVP-graft- AA nanogels

Poly(N-vinylpyrrolidone)-grafted-acrylic acid biocompatible nanogels (NGs) were prepared using an exiting industrial-type electron accelerator and setups, starting from semi-dilute aqueous solutions of a commercial PVP and the acrylic acid monomer. As a result, NGs with tunable size and structure can be obtained quantitatively. Sterility was also imparted at the integrated dose absorbed. The chemical structure of the NGs produced was confirmed through Fourier Transformer Infrared Spectroscopy (FT-IR). The molecular and physico-chemical properties of NGs, such as the hydrodynamic dimensions and surface charge densities, for various polymer and monomer concentrations in the irradiated solutio…

Polymeric Nanogels: Nanocarriers For Drug Delivery Application.

The application of nanotechnology to medicine has enabled the development of functionalised nanoparticles that, acting as carriers, can be loaded with drugs or genetic material to be released with a controlled mechanism in specific districts of the organism. Even though nanomedicine is a relative new branch of science, many type of nanocarriers for drug delivery have been developed over the past 30 years, such as liposomes, dendrimers, quantum dots, solid lipid nanoparticles, viruses and virus-like nanoparticles as well as a wide var iety of polymeric nanoparticles. Among these last, in our opinion, nanogels deserve a special attention. Nanogels are nanoscalar polymer networks, with a tende…

Synthesis and characterization of a new insulin conjugated nanogel for biomedical application

Insulin, a metabolic hormone involved in glucose metabolism, plays also a neuroprotective role in the central nervous system being able to revert the cytotoxic processes induced by Aβ42,a peptide involved in Alzheimer's disease. To reach the brain insulin have to across the BBB therefore an additional delivery strategy results to be necessary. For these aim we performed an insulin conjugated nanogels (NGs-In). Nanogels (NGs) have a great potential in the development of “smart” nanocarriers for (bio)molecular drugs and contrast agent for bioimaging. They are formed by physically or chemically crosslinked polymer networks, characterized by a large and flexible surface available for multivalen…

Preparazione di nanoparticelle di xiloglucano degalattosilato per applicazioni biomediche

Crosslinking of poly(vinylpyrrolidone) activated by electrogenerated hydroxyl radicals: a first step towards a simple and cheap synthetic route of nanogel vectors

A facile electrosynthesis route for the preparation of polymer nanogels based on the in situ production of hydroxyl radicals is reported for the first time. Electro-Fenton process with continuous H2O2 electrogeneration and Fe2+ regeneration performs better than electro-oxidation with a boron-doped diamond or dimensionally stable anode for promoting crosslinking of poly(vinylpyrrolidone). Keywords: Electrogenerated hydroxyl radicals, BDD, DSA, Electro-Fenton, Polymer modification, Nanogel

Temperature-responsive degalactosylated xyloglucans as nanocarriers for the sustained release of hydrophobic drugs

Inorganic/organic hybrid nanoparticles synthesized in a two-step radiation-driven process

In this work, we have synthesized inorganic-organic hybrid nanoparticles via radiation synthesis of inorganic nanoparticles (Ag and CeO2) in aqueous dispersions containing radiation-synthesized poly(N-vinyl pyrrolidone) (PVP) nanogels (NG). The experiments show that there are strong interactions between the inorganic precursors (Ag+ and Ce3+) and the nanogel prior to irradiation. The two hybrid systems (Ag/NG and CeO2/NG) were characterized using X-ray diffraction (XRD) and transmission electron microscopy (TEM). XRD confirms the formation of crystalline Ag and CeO2. TEM reveals that the inorganic nanoparticles are evenly distributed in/on the nanogel. Both XRD and TEM show that size of the…

Structure of e-beam sculptured poly(N-vinylpyrrolidone) networks across different length-scales, from macro to nano

Abstract Study of macromolecular structure and dynamics of networks formed by pulsed electron-beam irradiation of poly(N-vinyl pyrrolidone) (PVP) aqueous solutions, at relatively low energy per pulse and across different concentration regimes, provides the basis for the understanding of a new generation of functional nanostructures. Networks are the result of the follow–up reactions initiated by a continuous series of electron pulse-generated hydroxyl radicals, which may have a different fate at the variance of polymer concentration. Different spectroscopic techniques, FT-IR, 13 C { 1 H} CP-MAS NMR and Raman, applied to characterize the formed networks, describe a profound modification of t…

Radiation-Engineered Functional Nanoparticles in Aqueous Systems.

Controlled synthesis of nanoscalar and nanostructured materials enables the development of novel functional materials with fine-tuned optical, mechanical, electronic, magnetic, conductive and catalytic properties that are of use in numerous applications. These materials have also found their potential use in medicine as vehicles for drug delivery, in diagnostics or in combinations thereof. In principle, nanoparticles can be divided into two broad categories, organic and inorganic nanoparticles. For both types of nanoparticles there are numerous possible synthetic routes. Considering the large difference in nature of these materials and the elementary reactions involved in the synthetic rout…

Solid State NMR Spectroscopy Investigation of the Molecular Structure of Epoxy Based Materials Cured in Different Conditions

In this work two epoxy resin model systems, whose monomers are typically used in structural composites, were thermally cured in different cure conditions in order to obtain different cross-linking densities. Their molecular structures were investigated through solid state NMR spectroscopy in order to correlate them to the cure process conditions used and the results were discussed in the light of the dynamical mechanical thermal analysis (DMTA) performed.

Two electochemical methodologies for the synthesis of cyanoacetic acid

Oligonucleotides-decorated-poly(N-vinyl pyrrolidone) nanogels for gene delivery

Pulsed electron-beam irradiation of a semi-dilute poly(N-vinyl pyrrolidone) (PVP) aqueous solution in the presence of acrylic acid has led to a carboxyl functionalized nanogel system. Nanoparticles hydrodynamic size and surface charge density, in water and as a function of pH, were investigated by dynamic light scattering and laser doppler velocimetry, respectively. Nanogels (NGs) were proved not to be cytotoxic at the cellular level. Indeed, they rapidly bypass the cellular membrane to accumulate in specific cell portions of the cytoplasm, in the perinuclear area. The availability of pendant carboxyl groups on the crosslinked PVP NGs core prompted us to attempt their decoration with a sing…

Radiation-Engineering of All Plastic Nanocomposite Films

In recent years, polymer nanocomposites have fascinated scientists, engineers and industrialists on the premise that the creation of new and more performing polymeric materials is possible by the combination of different building blocks with controlled dimensions at the nanoscale. Unfortunately, uniform dispersion of the hetero-phase domains within the plastic matrix or on its surface often fails due to the unfavorable thermodynamics, thus resulting in migration and irreversible aggregation phenomena. In-situ generation of a dispersed hetero-phase within the same polymer matrix or in its precursors increases the chances of achieving a better control of morphology by eliminating the often cr…

A new route for the preparation of flexible skin–core poly(ethylene-co-acrylic acid)/polyaniline functional hybrids

Abstract Surface modification of polymeric films is a way to obtain final products with high performance for many specific and ad hoc tailored applications, e.g. in functional packaging, tissue engineering or (bio)sensing. The present work reports, for the first time, on the design and development of surface modified ethylene–acrylic acid copolymer (EAA) films with polyaniline (PANI), with the aim of inducing electrical conductivity and potentially enable the electronic control of a range of physical and chemical properties of the film surface, via a new “grafting from” approach. In particular, we demonstrate that PANI was successfully polymerized and covalently grafted onto flexible EAA su…

Sintesi di nanogeli per la veicolazione di insulina al cervello: una strategia per il trattamento della malattia di Alzheimer

I nanogeli sono nanoparticelle polimeriche reticolate idrofile. La struttura polimerica del nanogelo permette la coniugazione di molecole che possano esplicare azioni terapeutiche, diagnostiche e di indirizzamento attivo su siti bersaglio. Le caratteristiche di flessibilità e conformabilità del nanogelo, e delle sue maglie, ne favoriscono l’attraversamento delle barriere biologiche, l’interazione di eventuali ligandi esposti sulla superfice con i recettori target, un’azione protettiva nei confronti del principio attivo incorporato. L’irraggiamento con radiazioni ionizzanti di soluzioni acquose di polimeri è una metodologia sintetica interamente “water-based”, che garantisce rese elevate e c…

Insulin-nanogels: preliminary study in mouse for the treatment of Alzheimer's disease

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signalling are involved in brain cognitive functions and their dysfunction is implicated in Alzheimer’s disease (AD). Thus, administration of insulin could be a strategy for AD treatment. For this aim we have designed, synthesized and characterized a nanogel system (NG) that has been conjugated to insulin molecules (NG-In) (1) as new therapeutic approach against AD. In our preclinical studies in mice, intraperitoneal injection of fluorescent-labeled NG has allowed to determine the biodistribution of NG vs time in the whole body and its clearance through the kidneys and bladder. Furthermore, we have observed that mic…

Xyloglucan-based hydrogel films for wound dressing: Structure-property relationships

Thin xyloglucan-based hydrogel films have been synthetized and characterized in the prospect of producing wound dressings. Polyvinyl alcohol (PVA) and glycerol (Gro) were added to have an optimal combination of softness, conformability and resilience. Physical hydrogels have been transformed into permanent covalent hydrogels by reaction with glutaraldehyde (GA). Network structure-process-property relationships are discussed on the account of the results of several complementary characterizations: FTIR, rheology, thermal analysis, morphological analysis, moisture retention and swelling measurements. Selected formulations were also subjected to preliminary in vitro cytotoxicity tests. The phy…

Chemical design of flexible skin-core poly(ethylene-co-acrylic acid)/nanostructured polyaniline hybrids

In-situ polymerization of polyaniline in radiation functionalized polypropylene films

Abstract In-situ generation of a nanodispersed conductive polymer within a polypropylene matrix has been pursued in order to obtain flexible, conductive films. Radiation grafting of acrylic acid to polypropylene (PP) has been applied to insert carboxyl functionalities on PP. The radiation-grafted films have been further derivatized with a variety of diamines and used as substrates for in-situ chemical oxidative polymerization of polyaniline (PANI). PANI grows as a thin skin from the surface of the film as well as an interpenetrated network in its interiors. Evidence of chemical attachment of PANI to PP has been sought by performing FTIR and XPS analyses after extraction of the unbound polym…

Temporal control of xyloglucan self-assembly by radiation-induced degradation

Xyloglucan is a natural polysaccharide present as storage material in seeds and structural materials in the primary cells walls of higher plants. Xyloglucan from tamarind seed is composed of B(1,4)-D-glucan backbone, partially substituted by a-(1,6)-linked xylose units, some of which are B-D-galactosylated at O-2. In its native form the polymer is water-soluble and forms gel in the presence of moderate amounts of alcohols. When a given fraction of galactosyl residues are removed, the polymer acquires the ability to form gels in aqueous solution at physiological temperatures, a property of great interest for biomedical/pharmaceutical applications. Gelation on increasing temperature can be as…

Radiation processing: a versatile methodology to tune the structure of polymeric materials

RFID epidermal sensor including hydrogel membranes for wound monitoring and healing

This contribution experimentally demonstrates for the first time the feasibility of joint application of passive UHF RFID technology and hydrogel membranes to fabricate smart plasters able to gather and remotely transmit information on the conditions of human skin. In particular, this intelligent plaster is sensitive to temperature and fluid uptake/release and could open interesting scenarios in wound healing monitoring and drug delivery.

E-beam crosslinked nanogels conjugated with monoclonal antibodies in targeting strategies

Abstract Poly(N-vinyl pyrrolidone)-based-nanogels (NGs), produced by e-beam irradiation, are conjugated with monoclonal antibodies (mAb) for active targeting purposes. The uptake of immuno-functionalized nanogels is tested in an endothelial cell line, ECV304, using confocal and epifluorescence microscopy. Intracellular localization studies reveal a faster uptake of the immuno-nanogel conjugate with respect to the ‘bare’ nanogel. The specific internalization pathway of these immuno-nanogels is clarified by selective endocytosis inhibition experiments, flow cytometry and confocal microscopy. Active targeting ability is also verified by conjugating a monoclonal antibody which recognizes the αv…

Photonic crystal hydrogel films responsive to ethanol vapors

Gamma irradiation of xyloglucans and hydroxypropyl cellulose in dry and humid solid state to tune molecular weight distribution

Synthesis of cyanoacetic acid by carbon dioxide and electrogenerated acetonitrile anion in undivided cells equipped with sacrificial anodes

The electrochemical synthesis of cyanoacetic acid was performed by cathodic reduction of tetraalkylammonium salts (R4NX) in acetonitrile in undivided cells equipped with sacrificial anodes with concomitant or subsequent addition of carbon dioxide. These syntheses avoid the use of dangerous reagents, yield cyanoacetic acid in moderate faradic yields and confirm that the cathodic reduction of tetraalkylammonium salts in the presence of acetonitrile leads to the formation of the anion CNCH2-.

Development and characterization of xyloglucan-poly(vinyl alcohol) hydrogel membrane for wireless smart wound dressings

Research which addresses advanced wound management can contribute to the needs of modern healthcare, especially in situations that require continuous monitoring, analysis, responsive therapeutic treatments and data recording. The development of “smart” bandages and dressings that can remotely monitor relevant parameters for the wound healing process without a hospital intervention can be very useful tools for patients and physicians and for advancing the understanding of the healing process. In the present work, biocompatible xyloglucan/poly(vinyl alcohol) hydrogels are being developed as smart wound dressings that, in addition to the traditional favorable properties of hydrogels as skin ca…

DESIGN AND CHARACTERIZATION OF MUCOADHESIVE SUBLINGUAL FILMS CONTAINING FUROSEMIDE

Sintesi del coenzima Q10

Temporal control of xyloglucan self-assembly into layered structures by radiation-induced degradation

Partially degalactosylated xyloglucan from tamarind seeds (Deg-XG) is a very appealing biopolymer for the production of in situ gelling systems at physiological temperature. In this work, we observe that the morphology of hydrogels evolves towards high degrees of structural organization with time, yielding to dense stacks of thin membranes within 24 h of incubation at 37 °C. We also explore the possibility offered by gamma irradiation of controlling the time scale of this phenomenon, the final morphology and mechanical properties of the system. Structural and molecular modifications of Deg-XG with dose are investigated by FTIR, dynamic light scattering (DLS) and rotational viscosimetry. The…

Flexible nanoskin-core poly(ethylene-co-acrylic acid) polyaniline hybrids

Studies of network structure and dynamics of e-beam crosslinked PVPs: From macro to nano

Much interest has been paid to develop a variety of radiation-crosslinked hydrated polymeric materials, which swell in water but do not dissolve, as biocompatible materials used for wound healing, drug delivery system, surface-coating material for medically used devices, etc. With the aim of establishing design rules to produce hydrogels of controlled size at the nanoscale and desired internal network structure using conventional electron accelerators and set-ups, here we attempt a description in terms of structural and dynamic properties of polymer networks generated through e-beam irradiation of aqueous solutions of the same model polymer, a commercial grade poly(N-vinyl-pyrrolidone), sub…

Injectable xyloglucan hydrogels incorporating spheroids of adipose stem cells for bone and cartilage regeneration

Abstract Cartilage or bone regeneration approaches based on the direct injection of mesenchymal stem cells (MSCs) at the lesion site encounter several challenges, related to uncontrolled cell spreading and differentiation, reduced cell viability and poor engrafting. This work presents a simple and versatile strategy based on the synergic combination of in-situ forming hydrogels and spheroids of adipose stem cells (SASCs) with great potential for minimally invasive regenerative interventions aimed to threat bone and cartilage defects. Aqueous dispersions of partially degalactosylated xyloglucan (dXG) are mixed with SASCs derived from liposuction and either a chondroinductive or an osteoinduc…

Ibridi flessibili e conduttivi di poly(etilene-co-acido acrilico)/polianilina con struttura "nanoskin-core"

Numerical Simulations of Nanogel Synthesis Using Pulsed Electron Beam

In this work, a new method for numerical simulation of the radiation chemistry of aqueous polymer solutions exposed to a sequence of electron pulses is presented. The numerical simulations are based on a deterministic approach encompassing the conventional homogeneous radiation chemistry of water as well as the chemistry of polymer radicals. The multitude of possible reactions in the macromolecular system is handled by allowing for a large number of macromolecular species. The speciation of macromolecular species is done to account for variations in molecular weight, number of alkyl radicals per chain, number of peroxyl radicals per chain, number of oxyl radicals per chain, and number of in…

Hydrothermal aging of carbon reinforced epoxy laminates with nanofibrous mats as toughening interlayers

Electrospun mats have been applied as toughening interlayers in high performance carbon fiber epoxy composites. While the toughening mechanism exerted by the mat at the interface is the subject of several recent studies, no investigations are reported on the aging behaviour of laminates comprising these nanostructured elements. This work investigates the influence of the combined effect of water and temperature (90 °C) on laminates with Nylon 6,6 electrospun membranes placed either at the middle plane only or at each interlayer. The water-uptake behaviour is modelled by a two-stage diffusion model and compared with the behaviour of the neat resin and of the laminate without mats. Interestin…

Understanding generation of multifunctional nanogels in chemical-free e-beam irradation synthesis

Radiation engineered nanogels are the core of very promising theranostic nanodevoces. They can be produced starting from aqueous solutions of chemically inert polymers by pulsed e-beam irradiation.

Functional consequences of prey acclimation to ocean acidification for the prey and its predator

Ocean acidification is the suite of chemical changes to the carbonate system of seawater as a consequence of anthropogenic carbon dioxide (CO2) emissions. Despite a growing body of evidences demonstrating the negative effects of ocean acidification on marine species, the consequences at the ecosystem level are still unclear. One factor limiting our ability to upscale from species to ecosystem is the poor mechanistic understanding of the functional consequences of the observed effects on organisms. This is particularly true in the context of species interactions. The aim of this work was to investigate the functional consequence of the exposure of a prey (the mussel Brachidontes pharaonis) t…

Nanocarriers to targeted terapy: a goal for biomedical applications.

The reasons for the growing interest in biomaterials for application in the biomedical field are related to need to find alternative and more effective than conventional procedures used in drug treatment of several diseases. The traditional methods of drug delivery has limitations due to the drug’s toxicity in the body. The development of nanocarriers, which can be functionalized and loaded with drugs or genetic material and can be released into the body with a controlled mechanism, was a real goal in the field of biomedical applications. Synthetic hydrogels have found many applications especially in tissue-engineering scaffolds, as carriers for implantable and drug delivery devices. Hydrog…