Fabrication of drug-loaded biodegradable microcapsules for controlled release by combination of solvent evaporation and layer-by-layer self-assembly

Abstract

The initial burst release of drug from polymer microparticles remains an unsolved problem. Here, we deposited polysaccharides on drug-loaded microspheres using layer-by-layer self-assembly to produce core-shell microparticles for sustained drug release. The ibuprofen (IBU)-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microparticles were fabricated by conventional solvent evaporation. The processing parameters, such as pH of water phase, drug/polymer ratio, polymer type, and emulsifier concentration, were optimized according to the encapsulation efficiency and drug loading as pH 4.0, drug/polymer ratio=10/50 (wt), HV in PHBV=6wt.%, and PVA concentration=1% (w/v). The multilayer shells of chitosan (CHI)/sodium alginate (ALG) and poly(diallyldimethylammonium chloride) (PD)/sodium poly(styrenesulfonate) (PSS) were formed on the IBU-loaded PHBV microparticles using layer-by-layer self-assembly. The in vitro release experiments revealed that, as for the microparticles with three CHI/ALG bilayer shells, the initial burst release of IBU from the microparticles was significantly suppressed and the half release time was prolonged to 62h from 1h for the microparticles without coverage. The compact CHI/ALG multilayer film was observed with an atomic force microscopy (AFM) due to the matched distance of charges along the CHI chain and those along the ALG chains. The present combination for encapsulating drug-loaded microparticles demonstrates an effective way to prolong the drug release with reduced initial burst.