Solvent evaporation/extraction method is widely used for core-shell microspheres fabrication. However, the solvent evaporation rate, as an essential factor for polymers phase separation, is difficult to control which results in failure of complete phase separation between polymers. At the present study, the selective dissolution technique was used to improve the phase separation, and successfully fabricate core-shell microspheres for controlled delivery of drug with reduced initial burst release. The core-shell microspheres were prepared with poly(l-lactic-co-glycolic acid) (PLGA) and poly(l-lactic acid) (PLLA), and aspirin was used as model drug. Ethyl acetate (EtAc) was applied to ameliorate the phase separation during the preparation process. The ratio of dichloromethane (DCM)/EtAc seriously affected the distribution of polymer molecules and the formation of the core-shell structure. The internal morphology of the microspheres varied depending on the amount of EtAc. Core-shell structure with a dense core of PLLA and a shell of PLGA was well formed when 2 ml EtAc was used. The differential scanning calorimeters (DSC) results showed two distinct melting points which confirmed a completely polymer phased separation occurred. These microspheres showed sustained release of aspirin for at least 456 h with a little burst release (3.49%).
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