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The transparency of the cornea is maintained by the stem cells of the corneal epithelium in the limbal region; damage to the limbus may cause partial or total limbal stem cell deficiency that, may lead to blindness. The transplantation of cells is crucial to regenerate the damaged areas. The techniques currently employed consist in cadaveric corneal transplantation or in the use of amniotic membrane as a carrier for delivering cultured limbal stem cells to the cornea. Both these approaches show severe drawbacks such as the potential reject of the transplanted cornea and the risk of viral disease transmissions. Here we report the production of an electrospun device that could be exploited as a scaffold for the culture of corneal epithelial/stem cells and for their subsequent release onto the corneal surface. Such device is composed by a micro fibrillar electrospun mat covered by a polymeric film able, in vitro, to allow the attachment of the cells and to promote potentiallly, when implanted in vivo, their release onto the cornea as a result of a non invasive treatment. Polylactic acid was employed as starting material to obtain the structural basis of the device because of its peculiar mechanical properties that could facilitate its safe implantation onto the cornea. The coating was conducted by soaking the electrospun mat in a solution of a derivative of hyaluronic acid (named HA-EDA-C18) employed as film-forming reversible coating system. We demonstrated that HA-EDA-C18 film can be rapidly dissolved by treating it with a solution containing hydroxypropyl beta-cyclodextrin (HP-beta-cyd). Fibronectin was physically adsorbed onto the HA-EDA-C18 film to facilitate the in vitro attachment of corneal epithelial cells. In vitro studies reveal that, the device is able to release viable cells already 24 h after the treatment with HP-beta-cyd solution as a result of the coating film dissolution.

The topical route is the ideal way to release drugs to the eye. Unfortunately, the low ocular drug bioavailability associated with this route of administration, makes not very efficient the treatment of several ocular diseases. Nowadays, polymeric micelles occupy a significant role in the field of ocular drug delivery thanks to the advantages that they offer in comparison with the administration of drugs in the free form. Indeed, polymeric micelles are suitable for delivering hydrophobic drugs and they seem to be very promising in ocular drug delivery for their high kinetic and thermodynamic stability. Also, micellar systems are able to give a controlled drug release and to act as absorption enhancers that can improve drug permeability across ocular epithelia [1, 2]. To this aim, the objective of this study was to obtain new hyaluronic acid-based micellar systems capable to act as solubility enhancers and as a platform to release hydrophobic drugs to the eye. Three amphiphilic copolymers of hyaluronic acid bearing side chains of hexadecylamine (C16), named HA-C16 a, HA-C16 b and HA-C16 c with a molar derivatization degree equal to 15, 12 and 7% respectively, have been synthesised and characterized. The critical aggregation concentration (CAC) values of these amphiphilic copolymers was determined in water and isotonic buffer by fluorescence technique. Micellar systems have been obtained through co-solvent evaporation method and they have been characterized for physicochemical properties including size and zeta potential values. Also, different mucoadhesion tests have been performed to demonstrate the affinity of prepared micelles towards mucin. All HA-C16 derivatives have shown the ability of self-assembling in aqueous media and resulted potentially useful for encapsulating and dissolving hydrophobic drugs. In particular, dexamethasone and triamcinolone loaded micelles have been prepared and characterized using HA-C16 a, HA-C16 b and HA-C16 c copolymers. In vitro drug release studies have been carried out until 48 hours and results have demonstrated that micellar systems modulate drug release. At last, studies of cytocompatibility performed with human corneal epithelial cells (HCECs), have demonstrated that the prepared systems do not cause toxic effects.

In traditional ocular formulations, only small amount of the administered drug penetrates the cornea to reach the intraocular tissue. One approach to improve the drug ocular bioavailability was to develop colloidal drug delivery systems. Polymeric micelles seem to be very promising for their capacity to dissolve a variety of hydrophobic drugs by enhancing their water solubility and so their bioavailability. They are able to increase ocular drug permeability due to interact with the complex corneal structure. Considering the advantages to use mucoadhesive polymer to increase drug residence time on the ocular surface, the aim of this work was to prepare hyaluronic acid-based micelles as a platform to release corticosteroids on the ocular surface. Three amphiphilic derivatives of hyaluronic acid (HA), bearing different amount of hexadecylamine chains (C16), were synthesised and characterized. These are able to form micelles by using the co-solvent evaporation method. All HAC16 derivatives have shown the ability of durable mucoadhesive interactions and resulted potentially useful for corticosteroids encapsulation. Drug-loaded micelles were prepared and characterized in term of drug loading amount and particle size. Moreover, the in vitro drug release studies from micellar systems were carried out in comparison with the dissolution profile of the free drug suspension. Cytocompatibility studies also were performed with HCEpiC cells. HAC16b (DDC16mol%=12%) micelles are selected as the best nanosystems, and their capacity to improve the drugs permeability across corneal barrier are evaluated. Thus, the ex vivo permeation studies were conducted using bovine corneas and Franz type diffusion cells.

Conclusion: HA-g-PDLLA hydrogel is suitable to coat a prosthesis remaining adherent to it and distributing itself in the bone cavity. The hydrogel has been proven effective in a rabbit model of highly contaminated implant. In vivo studies have demonstrated how the intraoperative coating of implants with DAC is safe and feasible. HA-EDA-MA hydrogel is able to protect PEP from alteration during storage and it seems a good candidate for a potential once-daily oral formulation in the treatment of celiac disease.

Hyaluronic acid, celiac disease

With the high occurrence of cardiovascular disease and increasing numbers of patients requiring vascular access, there is a significant need for small-diameter (

In this paper, we present a one step plasma based approach for the deposition of Pt-fluorocarbon nanocomposite films as electrocatalysts in hydrogen-based micro fuel cells. Results show that the chemical and morphological structure of the film can be tuned by controlling the power delivered to the plasma, and the gas feed composition. Platinum is included in the film in metallic form and its content can be continuously varied from a few atomic percent to 86%. The metal is embedded in the film as crystalline nanoclusters of size below 10 nm, uniformly distributed across the sample. Film catalytic activity, in terms of hydrogen oxidation reaction, has been tested by cyclovoltammetry and it increases with the Pt loading, with a maximum specific electrochemical surface area of 94cm(2) center dot mg(-1), for film deposited on flat glassy carbon.

The catalytic activity of a lysozyme-based oenological preparation toward the specific substrates i) glycol chitosan, as a non-cellular synthetic substrate, and ii) Oenococcus oeni, as a microbial substrate for muramidase activity, was investigated in wine-like acidic medium (tartaric buffer, pH 3.2). The good reproducibility and reliability of results revealed that both substrates are useful for lysozyme kinetics studies. Both the chitinolytic and muramidase activity of lysozyme were affected by uncompetitive substrate inhibition. However, the O. oeni effect occurred at very high concentration with respect to the typical wine bacterial content, even when microbial population reaches its maximum growth level during malolactic fermentation. The optimum pH and temperature for lysozyme activity were very far from the usual wine handling conditions, but residual enzyme activity was observed at pH 3.2 and 20°C, confirming that the oenological application of lysozyme is a useful practice.

The atmospheric pressure plasma deposition of hydroxyl functionalized hydrocarbon films is reported in this work, with a reactor fed with water aerosol and ethylene. The effects of power and feed flow rates onto film chemistry have been investigated. Coatings produced with this approach can find application in the biomedical field, among others, as platforms for cell adhesion and proliferation. Results show that operating at 4 kHz provides a much higher amount of hydroxyl group in the coating compared with samples obtained at 11 kHz. After water immersion, the stability of the films and their amount of hydroxyl groups remain high. A simplified deposition mechanism is proposed.

In recent years there has been a growing interest for the development of tubular scaffolds employed to assist the replacement of small blood vessels. Materials designed for this purpose need to be biodegradable, have good mechanical properties and improve cell adhesion, proliferation and differentiation. To obtain biomaterials with these properties, electrospinning seems to be one of the most useful technique. Several biodegradable synthetic polymers or constituents of the extracellular matrix (ECM) have been electrospun showing optimal mechanical properties and biodegradability. However, such polymers are lacking in versatile chemical structure affordable to immobilize growth factors or chemokines. The glycosaminoglycan heparin is able to bind several growth factors like vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and, when grafted onto the scaffold surface it is able to attract cells thus improving their proliferation and differentiation. Aim of this research was the production and the preliminary in vitro biological characterization of a new biodegradable material, obtained by electrospun a polyaminoacid-graft-polyester copolymer. The electrospun biomaterial has been successfully grafted with heparin exploiting the better chemical reactivity of the polyaminoacid portions of the graft copolymer. Then its morphology has been investigated by scanning electron microscopy (SEM) and the potential biodegradability of the material has been studied until 60 days. Preliminary biological data in vitro, on human endothelial cells, show a good compatibility of the scaffold obtained by electrospinning, with regard to cell adhesion and proliferation. Experiments are in progress to evaluate the effects of heparin on cell differentiation.