Synthesis, physicochemical, rheological and in-vitro characterization of double-crosslinked hyaluronic acid hydrogels containing dexamethasone and PLGA/dexamethasone nanoparticles as hybrid systems for specific medical applications.

Injectable hydrogels and biodegradable nanoparticles are using in tissue engineering applications and drug delivery systems. To improve physiochemical properties of biomaterials and to develop their applications, hybrid systems consist of hydrogels, and biodegradable nanoparticles were synthesized. In this study, hybrid systems based on double crosslinked hyaluronic acid and PLGA/Dexamethasone sodium phosphate (PLGADEX) nanoparticles are designed and synthesized in several steps. At the first step, poly(l-lactide-co-glycolide) (PLGA) in a ratio of LLA:GA = 85:15 mol% was synthesized via ring-opening polymerization. Then, PLGADEX nanoparticles were synthesized in different ratios using the partially modified emulsification-diffusion method and fully characterized, and desirable nanoparticle was selected (PLGADEX20). At the second step, a double cross-linked hyaluronic acid (XHA) was prepared by mixing various ratios of amino-hyaluronic acid and aldehyde-hyaluronic acid in the presence of genipin. Finally, by mixing of various ratios of PLGADEX20 and Dexamethasone sodium phosphate (DEX) with different ratios of XHA, hybrid systems were prepared. Based on the characterization of hybrid samples and the release studies, hydrogels containing nanoparticles showed a controlled drug release, while the best sample with 3% of optimized nanoparticle was chosen. According to physiochemical and biological properties, these hybrid systems can be good candidates for anti-adhesion barriers, wound dressings, and novel drug delivery systems.