Preparation of porous and nonporous biodegradable polymeric hollow microspheres

A simple method to prepare various porous and nonporous hollow microspheres composed of poly(d,l-lactic-co-glycolic acid) using a water/oil/water (W/O/W) multiple emulsion solvent evaporation technique is described. The volume of the inner aqueous phase was varied to observe the effect on microsphere morphology. Hollow microspheres possessing dense, nonporous polymer shell layers were prepared when an initial inner aqueous phase volume fraction of 5.6% was employed, while an initial volume fraction of 22.7% resulted in hollow microspheres with porous surface structures. This appeared to be related to the morphological composition of a viscous polymer layer which developed during the early phase of rapid solvent removal. The formation of porous and nonporous polymer shell layers, determined by the inner aqueous phase volume, affected the rate of solvent removal. A complex series of kinetic events including polymer solidification and emulsion instability played an important role in determining the final morphology. Release of bovine serum albumin during solvent removal indicated that the microsphere morphology was a critical factor influencing the loading efficiency of the protein.