Carboplatin-loaded PLGA microspheres for intracerebral injection: formulation and characterization

Abstract

The purpose of this study is to prepare and characterize injectable carboplatin-loaded poly(D,L,-lactic-co-glycolic) acid copolymer (PLGA) microspheres for the intracerebral treatment of malignant glioma. The microspheres were prepared by an acetone/mineral oil emulsion and solvent evaporation method. Preparation variables were optimized and the following processing conditions resulted in the highest drug loading and best yields of the microspheres compared with those prepared with the other variables: the PLGA concentration was 8% (w/w) in the internal phase; the emulsifier (Span 80) concentration was 8% (w/w) in the external phase; the ratio of the internal phase: the external phase was 1:8; the stirring speed was 1500 rpm; the emulsion time was 15 min; the solvent evaporation time was 3.75 hr. Microspheres so prepared were analysed for size distribution, drug loading, in vitro release and morphological characteristics. The drug release in phosphate buffer solution started with a 10-day slow release period, followed by a fast near zero order release period from 12 to 22 days. The carboplatin release in brain homogenate was slower than in phosphate buffer solution. The morphological changes of the microspheres during the in vitro degradation correlated with the drug relase profile. In conclusion, the carboplatin-loaded PLGA microspheres were specifically prepared to meet the specification as an injectable and biodegradable brain implant.