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Hydrogel wound dressings can play critical roles in wound healing protecting the wound from trauma or contamination and providing an ideal environment to support the growth of endogenous cells and promote wound closure. This work presents a self-assembling hydrogel dressing that can assist the wound repair process mimicking the hierarchical structure of skin extracellular matrix. To this aim, the co-assembly behaviour of a carboxylated variant of xyloglucan (CXG) with a peptide amphiphile (PA-H3) has been investigated to generate hierarchical constructs with tuneable molecular composition, structure, and properties. Transmission electron microscopy and circular dichroism at a low concentration shows that CXG and PA-H3 co-assemble into nanofibres by hydrophobic and electrostatic interactions and further aggregate into nanofibre bundles and networks. At a higher concentration, CXG and PA-H3 yield hydrogels that have been characterized for their morphology by scanning electron microscopy and for the mechanical properties by small-amplitude oscillatory shear rheological measurements and compression tests at different CXG/PAH3 ratios. A preliminary biological evaluation has been carried out both in vitro with HaCat cells and in vivo in a mouse model.

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.

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-dependent fashion when manufacturing PVP-nanogels. In this presentation, the origin of nanogel size control and functionalization are discussed in relation to dose, dose rate, polymer concentration and chemical conditions. The latter can be directly altered by purging the solutions with N2O or N2 or indirectly through the formation of H2O2 in systems with low polymer concentration. The discussion is based on recent experimental work and kinetics simulations. this understanding offers a new dimension for the design and production of radiation-sculptured multifunctional nanocarriers from aqueous solutions of polymers. In addition, the inherent boundaries of these systems in terms of processing parameters are explored.

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 is investigated. The rheological properties of the gels obtained by adding ethanol to the polymer water solutions are also described. The effects of alcohol content, storage time and irradiation dose on gel strength are discussed.

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 carrier was demonstrated by absence of cytotoxicity, oxidative stress and mitochondrial dysfunction. Hemocompatibility was demonstrated by hemolysis, coagulation time, leukocyte proliferation and inflammatory response tests. By immonufluorescence measurements we demonstrated that insulin conjugated to the NG (NG-In) is preotected by protease degradation and is able to bind and activate insulin receptor bringing to trigger the insulin signalling via AKT activation. Moreover, to provide consistent evidence on the functionality of the conjugated insulin on the glucose levels, the effect of NG-In was tested in mice demonstrating that plasma glucose levels was reduced. Neuroprotection of NG-In against dysfunction induced by amyloid β, a peptide mainly involved in AD, was verified. Finally, the potential of NG-In to be efficiently transported across the Blood Brain Barrier was demonstrated by using an in vitro system. All together these results indicated that the synthesized NG-In was a suitable vehicle system for insulin delivery in biomedicine and a very promising tool to develop new therapies for neurodegenerative diseases. The research eas supported by MIUR, FLAGSHIP PROJECT NanoMAX.

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 che può conferire sterilità al prodotto. [1] Lo studio presentato illustra la possibilità di produrre nanogeli a base di polivinilpirrolidone con le caratteristiche desiderate in termini di dimensioni e con gruppi funzionali disponibili per reazioni di coniugazione con l’insulina. L’obiettivo è quello di realizzare un nanovettore in grado di veicolare l’insulina al cervello attraverso la mucosa nasale. Studi recenti hanno dimostrato che l’insulina è in grado di ridurre la tossicità del peptide beta amiloide (A, coinvolto nella patogenesi della malattia di Alzheimer (MA), e di esplicare una funzione neuroprotettiva. [2, 3] Sono state studiate le caratteristiche dimensionali del nanosistema, la biocompatibilità e la funzione di protezione dalla tossicità indotta da Anei confronti di cellule di neuroblastoma.

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, molecular weight and functionalization can be controlled by a proper selection of polymer concentration and irradiation parameters, such as dose-rate and total dose imparted [3]. In recent years, a growing body of evidence has linked insulin resistance and insulin action to Alzheimer’s Disease (AD), a condition also referred to as Type 3 Diabetes (T3D) [4,5]. Recently, it has been demonstrated that insulin is capable of reducing toxicity induced by A oligomers, the protein mainly involved in AD onset, by inhibition of the intrinsic apoptotic pathway [6]. Moreover, activation of insulin signaling provides a neuroprotective mechanism to counteract oxidative stress, mitochondrial damage and neurodegeneration triggered by A oligomers in neuroblastoma cells [7]. In the present work NGs have been conjugated to insulin (NG-In) to defend the hormone from enzymatic degradation, facilitate its crossing through a blood brain barrier model and protect the LAN5 cells from the damages induced by A oligomers addiction.

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 and through-puts by pulsed electron-beam irradiation. In particular, using an industrial electron accelerator, carboxyl functionalized NGs from a dilute aqueous solutions of poly(N-vinyl pyrrolidone) (PVP), and acrylic acid as functional monomer have been produced. This process allows simultaneous polymer cross-linking and monomer grafting. Moreover, depending on the value of the total irradiation dose, also the sterilization of the irradiated material can be obtained. Since organic solvents, toxic initiators or catalysts and surfactants are not required, this procedure can be defined as an eco-friendly and clean one. Crosslinked nanoparticles with multi-armed surfaces, and size, crosslinking density, and surface electric charge density controlled, have been generated. Nanogels produced have been proven to be hemocompatible and not cytotoxic or genotoxic at the cellular level. NGs have been decorated with fluorescent probes, proteins and anti-MiR. Thanks to the use of fluorescent variants, it has been argued that NGs showed a good affinity for cells, as they rapidly and quantitatively bypass the cellular compartments, accumulating in specific cell portions for the first hours, and being completely released from the cells in the next 24 hours. Moreover, it has been proven that the proteins and anti-MiR, once conjugated, maintain their biological activity giving rise to targeting features toward specific cell types.

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 polymer chains, such those based on high energy ionizing radiations or accelerated electrons which induce generation of free radicals on the polymer backbone (3). These active centers can undergo inter and/or intramolecular combination thus leading to the generation of a 3D network. Other authors have studied more simple methods to generate hydroxyl radicals in aqueous environment such as those based on Fenton reactions. On the other hand, electro-oxidation processes are well known to allow the abatement of recalcitrant organic compounds by the action of electro generated hydroxyl radicals (4). In this contest, we have focused the attention on three different electrochemical processes, characterized by different nature and reactivity of electrogenerated hydroxyl radicals: - Electro-generation of phisisorbed hydroxyl radicals at Boron Doped Diamond (BDD) “non-active anodes”; - Electro-generation of chemisorbed hydroxyl radicals at DSA (Ti/IrO2-Ta2O5) “active anodes”; - Electro-generation of homogeneous hydroxyl radicals by electro-Fenton (EF) Clear evidences of intramolecular crosslinking of poly(vinylpyrrolidone) macromolecular chains were obtained when the electrogeneration of homogeneous hydroxyl radicals was carried out by an electro-Fenton process. This reaction was confirmed by a reduction of the average gyration diameter of the chains in solution detected by dynamic light scattering accompanied by narrowing of the molecular weight distribution of the polymer. This is the first indication that an electrochemical method can be used to generate hydroxyl radicals that can be used to modify the molecular architecture of preformed polymers. Work is in progress to evaluate the effect of many operating parameters, such as flow dynamic regime, current density, working potential and temperature.

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 nm range (PDI

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 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 nm range (PDI

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 the polymeric aqueous solution and four insulin molecules per nanogel have been irreversibly attached. Absence of cytotoxicity, oxidative stress and mitochondrial dysfunction support the biocompatibility of the “naked” nanogels. Their hemocompatibility has been demonstrated by hemolysis, coagulation time, leukocyte proliferation and inflammatory response tests. By fluorescence measurements we have demonstrated that the insulin conjugated to the NG (NG-In) is protected by protease degradation and is able to bind and activate insulin receptor, thus triggering insulin signaling via AKT activation. In order to provide more significant evidence of the functionality of the insulin conjugated to the nanoparticles at the body level, the effect of NG-In in reducing the plasma glucose levels in mice has been demonstrated. Neuroprotection of NG-In against dysfunction induced by amyloid β, a peptide mainly involved in AD, has been also verified. Finally, the potential of NG-In to be efficiently transported across the Blood Brain Barrier has been demonstrated in vitro. All together, these results indicate that the synthesized NG-In is a suitable vehicle system for insulin deliver and a very promising tool to develop new therapies for neurodegenerative diseases

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 critical harvesting and re-dispersion steps in the manufacturing process. Strong interaction at the interface must be also provided to avoid aggregation and coarse phase-separation in usage. With this purpose, radiation grafting of a functional monomer onto polypropylene film has been applied to modify the molecular structure and properties of the otherwise chemically inert film. The radiation-grafted film has become permeable to the precursors of polymerization of a conducting polymer, namely polyaniline that can grow as a thin skin from its surface as well as an interpenetrated network into the film. Chemical attachment of the conducting polymer to the polyolefin has been demonstrated. The nanocomposite film shows an increase of electrical conductivity of several orders of magnitudes and amenability to be used as flexible electrode. In consideration of the well-known possibility of controlling the extent and depth of chemical modification of a substrate by radiation grafting, by tuning both system composition and irradiation conditions, this approach can enable a good degree of control of the morphology of the heterophase that forms on or within the substrate and thereby of the nanocomposite film. The recourse to suitable carriers, as chaperones of active molecules or nanoparticles into structurally different polymer matrices, is another possible strategy to obtain more uniform and stable dispersions. For this purpose, the possibility of obtaining colloidally stable micro-/nanoparticles from a partially degalactosylated xyloglucan (Deg-XG) has been investigated. 60Co γ-irradiation was applied to reduce the size of polymeric clusters in water. Irradiation was performed on the solid powder in air, up to a maximum dose of 60 kGy. FTIR and GPC analyses do not evidence any significant change of functional groups of the polymer and its average molecular weight, respectively. Deconvolution of GPC curves point to a change in the proportion between two main fractions of different molecular weight clusters, with a prevailing contribution of the lower over the higher MW clusters at the increase of the absorbed dose. Aqueous dispersions of the irradiated materials at low concentrations were characterized by dynamic light scattering measurements as function of the time and at different temperatures. For all systems an increase of scattered light intensity as function of the time at 37°C was observed. The fastest kinetics and the highest pseudo-plateau were shown by the 20 kGy irradiated system. Globular particles with 300-400 nm hydrodynamic diameters are formed. Their propensity to incorporate hydrophobic small guest molecules or high molecular weight biomolecules was assessed. The possibility of preparing optically transparent films from native xyloglucan incorporating these particles by solvent casting was demonstrated.

Aims and objectives Methods and materials Results Conclusion Personal information References, Aims and objectives: High dosages of (Gd3+)-based T1contrast agents (CAs) are required for MRI of tumors, in order to overcome the limitations due to their low sensitivity and inefficient accumulation at the target site, potentially causing sides effects or even sever...