Effects of preparation conditions of cisplatin-loaded microspheres on the in vitro release

Abstract

Microspheres from glycolide- l-lactide copolymers (PGLA) incorporating cis-diammine dichloroplatinum (II) (CDDP) were prepared with an O/O-type emulsion method to study the effects of the preparation conditions on the in vitro release of CDDP. PGLA was virtually immiscible with CDDP. Homogeneous dimethyl formamide (DMF) solutions of CDDP and PGLA were poured into liquid paraffin containing Span 80 as a surfactant, followed by solvent evaporation at elevated temperatures. DMF was used as the common solvent of PGLA and CDDP because it had the lowest boiling point of their conventional common solvents. The influencing factors studied in this work include rate of temperature rise, operating temperature for solvent evaporation, Span 80 concentration, the molecular weight of PGLA, CDDP loading and PGLA concentration. The effect of these preparation conditions on CDDP release was evaluated based on the observation of the resulting microspheres by scanning electron microscopy (SEM) and the plot of the amount of CDDP released against time. It was found that the operating temperature for the solvent evaporation and the rate of temperature rise to the operating temperature had a large effect on the release profile of CDDP. SEM observation of the cross-section of the microspheres revealed that the microsphere inside had a hole, although any significant deposit of micro-crystals of CDDP on the microsphere surface was not noticed.