Journal
PROGRESS IN POLYMER SCIENCE
Volume 32, Issue 8-9, Pages 962-990Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.progpolymsci.2007.05.009
Keywords
polymeric micelles; drug targeting; thermo-responsive micelles; ultrasound-responsive micelles; light-responsive micelles; ultrasound-enhanced chemotherapy
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Block copolymer micelles are generally formed by self-assembly of amphiphilic copolymer molecules in an aqueous milieu. The hydrophobic blocks (or polyion complexes) form the micelle cores while the hydrophilic blocks form the micelle corona (or shells). Consequently, lipophilic drugs are solubilized in the hydrophobic micelle cores, which dramatically increases drug concentration in an aqueous environment. This offers new life to bioactive compounds abandoned due to low aqueous solubility. Polymeric micelles can be designed to avoid extravasation to normal tissues and recognition by the reticulo-endothelial system cells; this prolongs their circulation time after systemic injection. This in turn provides passive targeting to cancerous or inflamed tissues via the enhanced permeability and retention effect. Active tumor-targeting may be achieved by modifying the micelle surface with specific ligands to tumor cell receptors or creating immunomicelles by attaching monoclonal antibodies to specific antigens over-expressed on the cancerous cell surface. A different approach to active tumor targeting consists of developing stimuli-responsive micelles that release their drug load only in response to environmental or physical stimuli, such as the lower pH in tumor tissue, heat, sound, or light. Currently, a number of polymeric micelles are in various phases of pre-clinical and clinical development. Present paper reviews recent advances in the development of physical stimuli-responsive micelles with high targeting potentials and controlled on-demand drug release. (C) 2007 Elsevier Ltd. All rights reserved.
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