In-vitro and in-vivo evaluation of pH-responsive polymeric micelles in a photodynamic cancer therapy model

pH-sensitive polymeric micelles of randomly and terminally alkylated N-isop ropylacrylamide copolymers were prepared and characterized. Aluminium chlor ide phthalocyanine (AlClPc), a second generation sensitizer for the photody namic therapy of cancer, was incorporated in the micelles by dialysis. Thei r photodynamic activities were evaluated in-vitro against EMT-6 mouse mamma ry tumour cells and in-vivo against EMT-6 tumours implanted intradermally o n each hind thigh of Balb/c mice. pH-sensitive polymeric micelles were foun d to exhibit greater cytotoxicity in-vitro than control Cremophor EL formul ations. In the presence of chloroquine, a weak base that raises the interna l pH of acidic organelles, in-vitro experiments demonstrated the importance of endosomal/lysosomal acidity for the pH-sensitive polymeric micelles to be fully effective. Biodistribution was assessed by fluorescence of tissue extracts after intravenous injection of 2 mu mol kg(-1) AlClPc. The results revealed accumulation of AlClPc polymeric micelles in the liver, spleen an d lungs, with a lower tumour uptake than AlClPc Cremophor EL formulations. However, polymeric micelles exhibited similar activity in-vivo to the contr ol Cremophor EL formulations, demonstrating the higher potency of AlClPc po lymeric micelles when localized in tumour tissue. It was concluded that pol ymeric micelles represent a good alternative to Cremophor EL preparations f or the vectorization of hydrophobic drugs.