In-vitro and In-Vivo Evaluation of pH-responsive Polymeric Micelles in a Photodynamic Cancer Therapy Model

J Pharm Pharmacol. 2001 Feb;53(2):155-66. doi: 10.1211/0022357011775352.


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 endosomalllysosomal acidity for the pH-sensitive polymeric micelles to be fully effective. Biodistribution was assessed by fluorescence of tissue extracts after intravenous injection of 2 micromol 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / chemistry*
  • Aluminum Chloride
  • Aluminum Compounds / chemistry*
  • Animals
  • Cell Survival / drug effects
  • Chlorides / chemistry*
  • Hydrogen-Ion Concentration
  • Mammary Neoplasms, Experimental / therapy
  • Mice
  • Micelles
  • Neoplasms / therapy*
  • Photochemotherapy / methods*
  • Polymers
  • Radiation-Sensitizing Agents / chemistry*
  • Tissue Distribution
  • Tumor Cells, Cultured


  • Acrylamides
  • Aluminum Compounds
  • Chlorides
  • Micelles
  • Polymers
  • Radiation-Sensitizing Agents
  • Aluminum Chloride
  • N-isopropylacrylamide