Creation ofPolumeric Drugs and Drug Carriers Possessing Pilot Molecules on the Surface and Their Application for Targeting Therapy

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We have been focusing on synthesis of several types of heterotelechelic poly(ethylene glycol), which denotes PEG possessing a functional group at one end and another functional group at the other chain end, both selectively and quantitatively. Utilizing these heteroPEG, lactose-PEG-SOD conjugate were prepared. The conjugate was found to incorporate preferentially to hepatocells such as HepG2 and HL60, via receptor mediated endocytosis.Using heteroPEG as macroinitiator for an anionic ring opening polymerization of lactide, PEG/PLA amphiphilic block copolymers possessing a functional group at PEG chain end were synthesized. The block copolymer forms core-shell type polymeric micelle in aqueous media having several tens nanometer size. The core-shell type polymeric micelle can solubilize hydrophobic drugs, which increases drug circulation in blood stream and reduces a toxicity of the drug due to the separation of the drug from the blood and tissues by the hydrophilic shell of the micelle. Consequently, polymer micelle-drug complexes show remarkable improvement in drug efficiencies, which is anticipated as one of the new nano-technology sciences for next generation.The most important point of the polymeric micelles thus prepared was the surface of the micelle. Since the PEG chain end locates on the periphery of the micelle, the surface should be functionalized by the PEG end group. Several ligands were installed on the surface of the PEG/PLA micelle. Finally, we observed specific interaction of the ligands on the micelle surface and receptor not only protein but also specific cells.On the basis of the investigations, new active targeting techniques will be opened.