Preparation and characterization of pH-responsive polymeric micelles for the delivery of photosensitizing anticancer drugs

pH-responsive polymeric micelles (PM) consisting of random copolymers of N-isopropylacrylamide (NIPA), methacrylic acid (MAA), and octadecyl acrylate (ODA) were prepared and characterized. The critical aggregation concentration, as determined by a fluorescence probe technique, was approximately 10 mg/L in water and phosphate-buffered saline. Phase transition pH was estimated at 5.7. The decrease in pH was accompanied by the destruction of hydrophobic clusters. Micelle size was-dependent on temperature and the nature of the aqueous medium. The micelles were successfully loaded with a substantial amount of a photoactive anticancer drug, namely, aluminium chloride phthalocyanine (AlClPc). ps-responsive PM loaded with AlClPc were found to exhibit higher cytotoxicity against EMT-G; mouse mammary cells in vitro than control Cremophor EL formulation. These results show the potential of poly(NIPA-co-MAA-co-ODA) for in vivo administration of water-insoluble, photosensitizing anticancer drugs. (C) 2000 Wiley Liss, Inc. and the American Pharmaceutical Association.