Preparation and Drug Sustained Release Behavior of Poly(?-caprolactone)/Poly(ethylene glycol)/Poly(?-caprolactone) Amphiphilic Block Copolymeric Microspheres Containing Biological Macromolecule / 中国药房

ABSTRACT

OBJECTIVE: To characterize morphology and drug release kinetics of protein-loaded poly(?-caprolactone)/poly(ethylene glycol)/poly(?-caprolactone) amphiphilic block copolymeric (PCE) microspheres, and elucidate the mechanistic details regarding protein release. METHODS: BSA-loaded PCE microspheres were prepared using a water-in-oil-in-water, followed by solvent evaporation. Morphology of the polymer microspheres was observed using scanning electron microscopy. Protein loading capacity and encapsulation efficiency were determined by extracting the proteins from the microspheres and measured using MicroBCA method. Protein release kinetics was characterized by cumulative release against the date of release incubation. RESULTS: The protein-loaded PCE microspheres were spherical and possess smooth surface under SEM. Protein loading capacity and encapsulation efficiency in the microspheres were independent of PCE molecular weight. However, the kinetic features of the protein release varied significantly with PCE molecular weight, suggesting a diffusion-degradation combined release mechanism. For the microspheres made of larger molecular weight PCE 4000, the portion of protein release attributed to diffusion from the polymer matrix was remarkably less than that from microspheres of small molecular weight PCE. In vitro release profile can be simulated using a diffusion-degradation model(Q=k1t1/2+k2t+k3t2+k4t3)(r=0.997). CONCLUSION: PCE microsphere formulation can offer sustainedrelease of proteins with initial burst and incomplete release reduced to acceptable level.