Injectable hydroxypropyl chitin hydrogels embedded with carboxymethyl chitin microspheres prepared via a solvent-free process for drug delivery

Microspheres and injectable hydrogels derived from natural biopolymers have been extensively investigated as controlled local drug delivery systems. In this study, we prepared carboxymethyl chitin microspheres (CMCH-Ms) with a diameter of 10-100 μm through physical crosslinking by increasing temperature in an aqueous two-phase system without using organic solvents, surfactants and crosslinking agents. The stable microspheres keeping spherical shape with porous microstructure in different pH environments were embeded in thermosensitive hydroxypropyl chitin (HPCH) hydrogels. The morphology, gelation rate, swelling, rheological and mechanical properties, in vitro degradation and cytotoxicity, drug loading and drug release of the CMCH-Ms/HPCH gel scaffolds were examined. In vitro degradation and cytotoxicity test indicated that CMCH-Ms/HPCH gel scaffolds were biodegradable and non-cytotoxic. Moreover, no organic solvent was used in the preparation and drug loading process of CMCH-Ms/HPCH gel scaffold. Importantly, less burst drug release and long-term sustained-release from the CMCH-Ms/HPCH composite hydrogel was observed than those from only CMCH-Ms or HPCH hydrogel. Thus, the composite CMCH-Ms/HPCH hydrogel exhibited great potential application for loading different drugs and sustained drug release in controlled local drug delivery systems.