Abstract
One of the fascinating subjects in areas such as materials science, nanochemistry, and biomimetic chemistry is concerned with the creation of supramolecular architectures with well-defined shapes and functions. Self-assembly of block polymers through non-covalent forces including hydrophobic and hydrophilic effects, electrostatic interactions, hydrogen bonding, and metal complication has great potential for creating such supramolecular structures. In particular, polymeric micelles formed in aqueous media through the self-assembly of block copolymers containing poly(ethylene glycol) (PEG) as the corona-forming segment have attracted considerable attention in the field of drug and gene delivery systems due to their excellent biocompatibility, long blood circulation time, and nontoxicity (Otsuka, Nagasaki &Kataoka, 2003). As can be seen in Figure 2.1, the number of publications on drug and gene delivery systems using block copolymer and PEG-based block copolymer is increasing significantly every year. Thus, the merits of PEG-based block copolymer have been becoming clearer to the research community every year. The PEG corona of the PEGylated polymeric micelles is believed to prevent recognition by a group of scavenger cells, viz., the reticuloendothelial system (RES) that is located mainly at the liver, the spleen, and the lungs. In addition, the increase in the apparent molecular mass by selfassembly of the block copolymers reduces clearance by renal excretion, resulting in prolonged blood circulation. Thus, the stealth effect of the PEG corona of the polymeric micelles is fairly effective in vivo. Indeed, a variety of nano-sized (< 100 nm) PEGylated polymeric micelles have been developed to precisely and safely deliver the appropriate concentrations of the anticancer drugs to tumor tissue, and some of these carriers have been approved for clinical use (Maeda, Sawa, & Konno, 2001) or are being studied currently in clinical trials, since they showed preferentially tumor accumulation caused by the enhanced permeability and retention (EPR) effect (Matsumura & Maeda, 1986). Furthermore, the installation of specific ligand molecules on the surface of PEGylated polymeric micelles
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