Abstract

Various cisplatin-loaded microsphere systems have been prepared from d,l-lactic acid stereocopolymers and d,l-lactic acid/glycolic acid copolymers using a solvent evaporation process. The morphology of these systems depends very much on different factors: addition of extra cisplatin in the dispersing phase, drug loading, polymer molecular weights and polymer concentration in the organic phase. In vitro release profiles have been determined for the various systems. It has been found that drug release depends on the amount of entrapped drug, on the presence of extra cisplatin in the dispersing phase, and on polymer molecular weights. In contrast, the release of cisplatin seems to be independent of the presence ofglycolic units within polylactic chains, and of radiosterilisation, although irradiation dramatically affected polymer molecular weights of completed microspheres. Results are discussed with respect to microsphere processing and morphology, especially cisplatin crystal distributions within the microspheres. It is concluded that the viscosity of the organic phase, in which the polymer is dissolved at the processing stage, is a critical factor. Data collected are discussed in terms of a predominantly diffusional release mechanism by either polymer matrices or dissolution in channels depending upon cisplatin crystal distribution in microspheres and, to some extent, upon polymer degradation.

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