Journal
REACTIVE & FUNCTIONAL POLYMERS
Volume 71, Issue 3, Pages 227-234Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.reactfunctpolym.2010.10.009
Keywords
Drug delivery; Polymeric micelle; Poly(ethylene glycol); Block copolymer; Polyion complex
Funding
- Grants-in-Aid for Scientific Research [22700489] Funding Source: KAKEN
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This review describes the design of polymeric micelles from block copolymers and their performances as nano-scale drug delivery systems, with emphasis on our recent work. The basic drug delivery system platform developed by our group consists of polymeric micelles comprising a core-shell structure with a versatile drug-loading hydrophobic core and biocompatible hydrophilic shell, and are several tens to one hundred nanometer in size. These characteristics are preferable to bypass both renal clearance and entrapment by the reticuloendothelial system, thus allowing subsequent accumulation within tumor tissues by the enhanced permeability and retention effect. Furthermore, polymeric micelles may be designed for enhanced biological performance by modification of the block copolymers to contain chemistries that can sense a specific biological environment. These smart micelles allow for target site-triggered drug release by reversible stabilization of the micelle structure and controlled intracellular trafficking (efficient endosomal release). Smart micelles designed with responsive features have demonstrated the utility in many cases compared to controls lacking such functionality. Additionally, the ability to control the size of polymeric micelles in the range of several tens to hundreds of nanometer significantly affects their longevity in the blood stream and efficiency of tumor tissue accumulation and penetration. In hypovascular tumor tissues, smaller polymeric micelles are more effective for tissue accumulation/penetration, bringing about stronger anti-tumor activity. All together, fine-tuning the structure of block copolymers enables preparation of polymeric micelles with versatile functions for treatment of many diseases including intractable cancer. (C) 2010 Elsevier Ltd. All rights reserved.
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