Biodegradable polymer/hydrogel composite for controlled delivery of cationic formulations

Abstract

Composites of biodegradable polymers and hydrogels are promising materials for controlled delivery systems with prolonged drug release. In this contribution, we present an innovative implant design comprising poly(DL-lactide-co-ε-caprolactone) copolymer base and a crosslinked poly(acrylic acid) hydrogel. Implants were prepared in the form of disks using the modified traditional liquid phase inversion process. Solutions containing all implant precursors were dispensed into transparent non-stick molds and cured by UV irradiation. UV curing was followed by immersion into the phosphate buffer solution bath to achieve phase separation and solidification. Structure and composition of the implant were characterized using SEM and FTIR. Obtained implants exhibited high loading capacity for cationic formulations and a moderate degree of swelling. Studies of implant loading and subsequent release of methylene blue into the phosphate-buffered saline demonstrated diffusioncontrolled delivery kinetics over a period of several weeks. To assess biocompatibility of implants as possible materials for drug delivery systems in mammals, we evaluated their effects on viability (Trypan blue exclusion assay), metabolic activity, proliferation (MTT assay) and priming (nitric oxide/NO production) of freshly isolated rat splenocytes during 24 h and 48 h of cultivation. The viability was unaltered, metabolic activity/proliferation was increased after 48 h and the decrease of NO production, as well as drop in responsiveness to cell mitogen concanavalin A (ConA) in cells on implants were observed. These results suggest that implants could be used as a suitable material for drug delivery systems, but their capacity to stimulate cell proliferation and their immunosuppressive potential deserve further investigations.