Insights into the reaction of chondroitin sulfate with glycidyl methacrylate: 1D and 2D NMR investigation.

Chondroitin sulfate methacrylate (CS-MA) is a semisynthetic biopolymer increasingly used for the fabrication of chemical hydrogels. In this study, the methacrylation reaction of native CS was carried out with glycidyl methacrylate in dimethyl sulfoxide and optimized to obtain tunable and reproducible methacrylation degrees in a short reaction time. The methacrylation reaction was deeply characterized by mono- and bi-dimensional (1D, 2D) NMR spectroscopy of CS-MA derivatives with different methacrylation degrees. In contrast to what previously reported in the literature, HSQC, HMBC and TOCSY analyses revealed that the methacrylation reaction proceeds via both epoxy ring-opening and transesterification, involving predominantly the primary hydroxyl groups of CS, while preserving sulfate and carboxyl groups of the biopolymer. These findings are of fundamental importance for appropriate and rational design of CS-MA-based biomaterials.

Solvent Casting and UV Photocuring for Easy and Safe Fabrication of Nanocomposite Film Dressings.

The aim of this work was to optimize and characterize nanocomposite films based on gellan gum methacrylate (GG-MA) and silver nanoparticles (AgNPs) for application in the field of wound dressing. The films were produced using the solvent casting technique coupled with a photocuring process. The UV irradiation of GG-MA solutions containing glycerol as a plasticizer and different amounts of silver nitrate resulted in the concurrent crosslinking of the photocurable polymer and a reduction of Ag ions with consequent in situ generation of AgNPs. In the first part of the work, the composition of the films was optimized, varying the concentration of the different components, the GG-MA/glycerol and GG-MA/silver nitrate weight ratios as well as the volume of the film-forming mixture. Rheological analyses were performed on the starting solutions, whereas the obtained films were characterized for their mechanical properties. Colorimetric analyses and swelling studies were also performed in order to determine the AgNPs release and the water uptake capacity of the films. Finally, microbiological tests were carried out to evaluate the antimicrobial efficacy of the optimized films, in order to demonstrate their possible application as dressings for the treatment of infected hard-to-heal wounds, which is a demanding task for public healthcare.

Injectable and In Situ Gelling Dextran Derivatives Containing Hydrolyzable Groups for the Delivery of Large Molecules.

Recently, we reported the synthesis and characterization of a new dextran derivative obtained by grafting polyethylene glycol methacrylate to a polysaccharide backbone through a carbonate bond. This moiety was introduced because it allows for the fabrication, through a photo-induced crosslinking reaction, of biodegradable hydrogels particularly suitable for the release of high molecular weight molecules. Here, we investigate the influence of the oxyethylene chain length and the molecular weight of the starting dextran on the main properties of the polymeric solutions as well as those of the corresponding hydrogels. All synthesized polymeric derivatives were characterized by FTIR, NMR, and rheological analyses. The photo-crosslinking reaction of the polymers allowed us to obtain biodegradable networks tested for their mechanical properties, swelling, and degradation behavior. The results showed that both the oxyethylene chain length as well as the molecular weight of the starting dextran influenced swelling and degradation of the hydrogel network. As a consequence, the different behaviors in terms of swelling and degradability were able to affect the release of a large model molecule over time, making these matrices suitable candidates for the delivery of high molecular weight drug substances.

Enhanced Loading Efficiency and Mucoadhesion Properties of Gellan Gum Thin Films by Complexation with Hydroxypropyl-ß-Cyclodextrin.

Polymeric oral thin films (OTFs) were prepared by the casting method, combining gellan gum (GG), a water-soluble polysaccharide, and glycerol (Gly) as a plasticizing agent. GG-Gly films were investigated as potential systems for buccal drug delivery using fluconazole (Class I of the Biopharmaceutical Classification System) as a model drug. At a low concentration of Gly drug precipitation occurred while, for higher concentrations of Gly, a significant deterioration of mucoadhesive and mechanical properties was observed. One possible way to overcome all these problems could be the addition of hydroxypropyl-ß-cyclodextrin (HP-ß-CD) to the GG-Gly formulation as a drug-precipitation inhibitor. In this work the effect of cyclodextrin addition on the mechanical, mucoadhesive, swelling and release properties of GG-Gly films was investigated. In-vitro drug release studies were carried out using the paddle type dissolution apparatus (USP II) and the millifluidic flow-through device (MFTD). A moving-boundary model for swelling dynamics and release in USP II is proposed to estimate the effective diffusivity of the solvent, HP-ß-CD, fluconazole and complex fluconazole/HP-ß-CD in the swelling film. Experimental results, supported by theoretical modeling, confirmed that gellan gum-low glycerol thin films including HP-ß-CD represent a suitable formulation for fluconazole drug delivery. A sustained release was observed when GG-Gly film is loaded with a preformed complex fluconazole/HP-ß-CD.