PLGA sustained-release microspheres loaded with an insoluble small-molecule drug: microfluidic-based preparation, optimization, characterization, and evaluation <i>in vitro</i> and <i>in vivo</i>

Abstract

Microspheres play an important role in controlling drug delivery and release rate accurately. To realize the sustainable release of insoluble small-molecule drugs, a new three-phase flow-focusing microfluidic device was developed to produce the drug-loaded sustained-release microspheres which were prepared with bicalutamide (BCS class-II) as the model drug and poly(lactide-co-glycolide) (PLGA) as the carrier material. Under optimized prescription conditions, the microspheres showed a smooth surface and uniform size of 51.33 μm with a CV value of 4.43%. Sustained-release microspheres had a releasing duration of around 40 days <i>in vitro</i> without any initial burst release. The drug release mechanism of the microspheres was drug diffusion and polymer erosion. Meanwhile, the drug release of microspheres <i>in vivo</i> could be up to 30 days. Briefly, the microfluidic device in this study provides a new solution for the preparation of sustained-release microspheres for insoluble small-molecule drugs. PLGA sustained-release microspheres developed by the microfluidic device have good application prospects in precise delivery and sustainable release of insoluble small-molecule drugs.