Facile control of porous structures of polymer microspheres using an osmotic agent for pulmonary delivery

It has been challenging to prepare polymeric microspheres with controlled porous structures for many biomedical applications, particularly for pulmonary drug delivery. Here, we report the use of bovine serum albumin (BSA) as an osmotic agent in order to control the porous structure of poly(D,L-lactide-co-glycolide) (PLGA) microspheres prepared by a double emulsion method. BSA was useful to induce osmosis between internal and external water phases during the double emulsion process, resulting in the fabrication of microspheres with controllable, uniform porous structures. The pore size of PLGA microspheres was controlled independently from the particle size by this approach. The use of BSA as an osmotic agent reduced the initial burst of model proteins (e.g., insulin and VEGF) entrapped in the porous microspheres, and the sustained release of VEGF was achieved for two weeks in vitro. This approach to controlling porous structures of polymer microspheres could be useful to develop novel pulmonary drug delivery systems.