Biodegradable Cisplatin Microspheres for Direct Brain Injection: Preparation and Characterization

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Abstract
The objectives of the present study were to prepare cisplatin loaded-PLGA microspheres that are suitable for direct brain injection and to characterize them in terms of their physicochemical properties, in vitro drug release, and self-removal mechanism. The microspheres were prepared by emulsification/solvent evaporation method using PLGA (50:50) as the biodegradable matrix forming polymer. The physicochemical characterization encompassed the following: surface morphology, particle size, entrapment efficiency, surface area, and density. The in vitro release and in vitro degradation studies were performed in phosphate buffer and in 10% rat brain preparation. SEM micrographs revealed that the microspheres have a rough porous surface and a smooth interior. Particle size typically ranged from 180 to 250 microns with an average of 230 T microns. Entrapment efficiency was approximately 70% and was found to be dependent on the particle size. Surface area and density ranged from 0.038 to 0.025 m2/g and from 1.44 to 1.39 g/cm3, respectively. Both were also dependent on particle size. In the in vitro release study in phosphate buffer, approximately 80% of cisplatin was released over 30 days, after which the release rate plateaued. The release profile in 10% rat brain preparation was comparable in shape to that obtained in phosphate buffer. However, the release rate was lower and the total amount released by the end of the study was only 55% of the total cisplatin content. The degradation of PLGA microspheres in phosphate buffer and in rat brain homogenate correlated well with the respective release profiles. Based on the evidence of self-removal and the sustained release of cisplatin for over a month, cisplatin-loaded PLGA microspheres may be useful for local delivery to brain tumors.