Multilayered drug delivery coatings composed of daidzein-loaded PHBV microspheres embedded in a biodegradable polymer matrix by electrophoretic deposition

Abstract

The development of drug delivery coating systems for local and long-term drug release is gaining increasing interest especially to functionalize bioinert implants with osseointegration and antibacterial properties. In this study, a biodegradable drug delivery coating platform consisting of drug-loaded PHBV microspheres embedded in an alginate–PVA matrix was fabricated by a one-step electrophoretic deposition (EPD) process. Layer by layer (LbL) deposition was exploited to generate chitosan–alginate multilayers on the EPD-produced coating to enlarge the diffusional barrier around the microspheres for controlled drug release. Daidzein, selected as a model drug due to its anti-osteoporosis properties, was pre-encapsulated in PHBV microspheres. The parameters for microsphere fabrication were optimized by an orthogonal design approach. The loading efficiency of daidzein in both the microspheres and in the deposited coatings was adjusted by varying the processing parameters during microsphere fabrication and the EPD process. The degradation of the deposited multilayers was investigated in PBS for up to 14 days. The degradation rate, surface roughness and wettability, as well as adhesion strength of the coatings during degradation were evaluated by applying a range of techniques. A controlled and sustained daidzein release was detected from both free microspheres and microsphere-containing coatings. Finally cytotoxicity and stimulatory effects of daidzein or daidzein-loaded coatings, on both MC3T3-E1 and RAW264.7 cell lines, were studied to validate the potential of the developed coatings for orthopedic applications.