Preparation and characterization of porous biodegradable microspheres used for controlled protein delivery

In this study, a new approach for protein delivery is introduced, involving biodegradable porous poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres blocked with calcium alginate hydrogel. Porous microspheres were prepared by solvent evaporation method using sodium oleate as an extractable porogen. The resultant microspheres show porous surface and three-dimensional network structure with interconnecting pores. Human serum albumin (HSA) used as model protein, was adsorbed into micropores of porous microspheres by a solution immersing method. Thus, the harsh preparation conditions, such as the aqueous/organic interface produced by a water-in-oil microemulsion and the acute shearing strength brought by a high-speed homogenizer or a sonicater, inducing protein denaturation and aggregation could be avoided. Then, calcium alginate hydrogel was fabricated to block micropores of protein-loaded porous microspheres. A sustained protein release in vitro could be achieved in this way. Furthermore, it is noteworthy that the protein maintained its structural integrity after this preparation. The porous polymeric microspheres may have great potential application for water-soluble drugs, such as protein, vaccine and gene delivery.