IngentaConnect In-vitro and in-vivo evaluation of pH-responsive polymeric micell...

Authors: Taillefer J.¹; Brasseur N.²; van Lier J.E.²; Lenaerts V.³; Le Garrec D.¹; Leroux J.C.¹

Source: Journal of Pharmacy and Pharmacology, Volume 53, Number 2, 1 February 2001 , pp. 155-166(12)

Abstract:

pH-sensitive polymeric micelles of randomly and terminally alkylated N-isopropylacrylamide copolymers were prepared and characterized. Aluminium chloride phthalocyanine (AlClPc), a second generation sensitizer for the photodynamic therapy of cancer, was incorporated in the micelles by dialysis. Their photodynamic activities were evaluated in-vitro against EMT-6 mouse mammary tumour cells and in-vivo against EMT-6 tumours implanted intradermally on each hind thigh of Balb/c mice. pH-sensitive polymeric micelles were found to exhibit greater cytotoxicity in-vitro than control Cremophor EL formulations. In the presence of chloroquine, a weak base that raises the internal 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

mol kg^-1 AlClPc. The results revealed accumulation of AlClPc polymeric micelles in the liver, spleen and lungs, with a lower tumour uptake than AlClPc Cremophor EL formulations. However, polymeric micelles exhibited similar activity in-vivo to the control Cremophor EL formulations, demonstrating the higher potency of AlClPc polymeric micelles when localized in tumour tissue. It was concluded that polymeric micelles represent a good alternative to Cremophor EL preparations for the vectorization of hydrophobic drugs.

Document Type: Research article

DOI: 10.1211/0022357011775352

Affiliations: 1: Faculty of Pharmacy, University of Montreal, Montreal (Qc) 2: MRC Group in the Radiation Sciences, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine, University of Sherbrooke, Sherbrooke (Qc) 3: Labopharm Inc., 1200 Chomedey Blvd, Suite 500, Laval (Qc), Canada H7V 3Z3

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