IN-VITRO AND IN-VIVO EVALUATION OF TAXOL RELEASE FROM POLY(LACTIC-CO-GLYCOLIC ACID) MICROSPHERES CONTAINING ISOPROPYL MYRISTATE AND DEGRADATION OF THE MICROSPHERES

This study describes the release and degradation profiles of taxol-loa ded poly(lactic-co-glycolic acid) microspheres containing isopropyl my ristate (IPM), namely, Taxol-IPM-PLGA-MS, in vitro and in vivo. Incorp oration of IPM into the PLGA microspheres effectively increased the re lease of taxol from the microspheres in vitro. The molecular weight (M el. Wt) and copolymer ratio of lactic acid (LA) and glycolic acid (GA) displayed obvious influences on the characteristics of the microspher es and their in vitro release kinetics. A large number of micropores c ould be observed on the surface of the microspheres and the number of these pores tended to increase with the increment of Mel. Wt. and LA c ontent of PLGA. This trend was in accordance with the rate of drug rel ease from the microspheres in vitro. Moreover, the degradation of PLGA matrix in vitro was retarded by the incorporation of IPM to a less ex tent compared with its effect on the drug release. Therefore, the drug diffusion in the matrix was shown to be an important factor dominatin g the release rate, while the degradation rate of the polymer is a mod erate factor in this case. Consistent with the in vitro results, the t axol concentrations in the lung after intravenous injection of the Tax ol-IPM-PLGA-MS were 2-4 times higher over one week, as compared with t hose after injection of the microspheres without IPM. In conclusion, t he Taxol-IPM-PLGA-MS may have great advantage in cancer chemotherapy a fter targeted delivery to a tumor site by chemo-embolization. (C) 1997 Elsevier Science B.V.