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Poly(ester)–graft–Poly(γ–glutamic acid) 兩性高分子之製備及其做為癌症藥物載體之應用
Thesis

Poly(ester)–graft–Poly(γ–glutamic acid) 兩性高分子之製備及其做為癌症藥物載體之應用

張國勇
Masters, National Tsing Hua University
2009

Abstract

聚麩胺酸聚乳酸/聚甘醇酸共聚物兩性高分子藥物釋放 Poly(γ–glutamic acid)poly[lactide-co-glycolide], PLGAamphiphilic copolymerdrug delivery
The colorectal cancer is the third death reason of the cancer in Taiwan, and the second in the world. The greatest defects of the anticancer drug for chemotherapy are able to kill normal cells but also cause the damage of the normal tissues or organs at the same time. Furthermore, the cancer cells can resist anticancer drug by themselves or through gene mutation by chemotherapy, resulting in forming drug resistances and losing the effect of the drugs. The main goal of this research is to develop a novel method of polymerization using an anticancer drug as the initiator, which produces nano-scale micelles with two kinds of anticancer medicines to overcome above defects. These micelles will kill cancel cells effectively and improve healing efficiency.First, an anticancer drug (5’DFUR) is utilized directly to be an initiator in the polymerization, and ε-caprolactone or (lactide/glycolide) is polymerized to form the 5’DFUR-poly(ε-caprolactone) (5’DFUR-PCL) or 5’DFUR-poly (lactide-co-glycolide)(5’DFUR-PLGA) in this study. The 5’DFUR-PCL and 5’DFUR-PLGA are then grafted to Poly (glutamic acid) (γ-PGA) to form a comb-like amphiphilic copolymers respectively (5’DFUR-PCL-γ-PGA and 5’DFUR-PLGA-γ-PGA). The characteristics of the copolymers will be examined by FT-IR, NMR and GPC. Additionally, a second anticancer drug is coated on micelles of amphiphilic copolymers by self-assembly method in aqueous phase to from a micelle with two kinds of the anticancer medicines. The effects of drug delivery and cure of colorectal cancer in vitro will be investigated.We expect that this novel polymerization method is able to replace the present technique, which would decrease the steps of the preparation process and reduce the prime cost; on the other hand, the nano-micelles carriers are designed from the concept of the cocktail therapy, might provide a way to cure effectively the colorectal cancer.

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