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, aluminum chloride phthalocyanine (AlClPc). pH-responsive PM loaded with AlClPc were found to exhibit higher cytotoxicity against EMT-6 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.
Taillefer
J
J
Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada H3C 3J7.
Jones
M C
MC
Brasseur
N
N
van Lier
J E
JE
Leroux
J C
JC
D000178:Acrylamides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008823:Micelles; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014867:Water
D000178:Acrylamides; D000970:Antineoplastic Agents; D007211:Indoles; D008823:Micelles; C112703:NIPAM-ODA copolymer; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011109:Polymethacrylic Acids; D013501:Surface-Active Agents; D014867:Water; C085085:poly(N-isopropylacrylamide-co-methacrylic acid); C060570:aluminum phthalocyanine; C000515:cremophor EL; C067295:N-isopropylacrylamide; D005990:Glycerol