Release mechanisms of bovine serum albumin loaded-PLGA microspheres prepared by ultra-fine particle processing system

The ultra-fine particle processing system (UPPS) previously developed by our lab has been used to prepare various microparticulate formulations. Microspheres prepared by UPPS can achieve sustained release with a reduced initial burst compared to the microspheres prepared by the conventional water-in-oil-in-water (W/O/W) double emulsion technique. However, the in vitro drug release mechanism of the microspheres prepared by UPPS is still uninvestigated. This study aimed to investigate the mechanisms of bovine serum albumin (BSA) released from poly (D,L-lactic-co-glycolic acid) (PLGA) microspheres prepared by UPPS in comparison with microspheres prepared by the W/O/W double emulsion technique. The morphology, in vitro drug release, water uptake, and structural evolution of microspheres prepared by both techniques were evaluated. UPPS microspheres showed solid and compact internal structures without any pores or channels thereby exhibiting a reduced rate of water permeation in the release medium. In addition, the release of BSA in UPPS microspheres was mainly controlled by the erosion of the polymer matrix during the entire process, while BSA was released from W/O/W microspheres by both drug diffusion and matrix erosion. Moreover, the observed surface and internal structural evolution also confirmed their different release mechanisms. This work elaborates the release mechanism of PLGA microspheres prepared by UPPS and facilitates the design of microparticulate formulations. Graphical abstract.