Uniform double wall microspheres/microcapsules for protein delivery

Abstract

Biodegradable polymer devices have been utilized as a means to deliver drugs in a controlled and less invasive manner. Poly (lactide-co-glycolide) (PLG) and poly (lactic acid) (PLA) microparticles such as double-wall/single-wall microspheres and microcapsules were heavily investigated for controlled delivery of small molecule drugs as well as proteins and DNA. The size distribution of protein-loaded biodegradable polymer microparticle is a crucial factor for allowable routes of administration. Also, the geometric structures of microparticles can influence the resulted release profile. In this project, by using the Precision Particle Fabrication method, we produced uniform double-wall microspheres (DWMS) with a protein-loaded (Bovine Serum Albumin) PLG core and a drug-free PLA shell, which was expected to provide better encapsulation of the protein as well as to postpone the protein release. Different inherent viscosity (i.v.) of PLG and PLA and different organic solvent configurations were used to produce uniform DWMS. Also, by studying the in vitro release profiles and microscopy images, we found that using ethyl acetate as shell-phase solvent, dichloromethane as core-phase solvent and using lower PLG and PLA i.v., better encapsulation of the protein-loaded core as well as clearly core-shell structure can be achieved. We have also successfully produced uniform protein-loaded DWMS with different shell thickness.