臺灣博碩士論文加值系統

作為藥物輸送系統來提高藥物的治療功效形式相當多種，而近年來高分子奈米微胞 (polymeric micelle) 已被越來越多的研究指出，能夠作為水難溶解性藥物的輸送載體，而一般常見的高分子奈米微胞通常由兩性共聚物 (amphiphilic copolymer) 構成。本研究目的在於設計兩性共聚物高分子形成奈米微胞，疏水端的部分能包覆藥物形成核心，而以樹枝狀聚合物設計的親水端也能供藥物的裝載，使其具備更高的載藥量與穩定性，由於此藥物載體具有兩種不同高分子材料，因此也會有兩種不同的藥物釋放速率。本研究利用生物可分解材料 poly(lactide-co-glycolide)(PLGA) 與不同世代 (generation) 之樹枝狀聚胺基甲酸酯 (G 2.0 PUAD、G 3.0 PUAD) 以脫水合成的方式，形成兩性共聚物。利用傅立葉紅外線光譜 (FT-IR) 與核磁共振光譜儀 (NMR) 確定其化學結構。並進行以下之性質研究：DLS與TEM粒徑分析、細胞毒性、藥物溶解度、藥物負載及藥物釋控。

Drug delivery system to improve the efficacy of treatment have a considerable types. In recent years some studies indicate that polymer nano-micelles can be used as delivery vehicles for drug with lower solubility. Polymeric micelles usually consists of amphiphilic copolymer. The purpose of this study is to design amphiphilic copolymer to form polymeric micelles. Hydrophobic side of the copolymer form the core, and then dendrimer hydrophilic end stabilize the particles in the aqueous medium. The amphiphilic copolymer was obtained through the reaction between the PLGA and different generation polyurethane dendrimers (PUAD) via dehydration. The chemical structure of the amphiphilic copolymer was indentified by fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). We also studied various properties about the synthesized amphiphilic copolymer as DLS and TEM to determine particle size, cytotoxicity, the increasement of drug solubility, drug loading, and controlled release.

摘要 I
ABSTRACT II
目錄 III
圖目錄 VII
表目錄 X
縮寫表 XI
第一章 緒論 1
1-1醫藥高分子材料 1
1-2 奈米技術的運用 1
1-3 藥物輸送系統 2
1-4 Micelles發展 3
1-5 Mixed micelle 5
1-6 微胞之製備 6
1-7 樹枝狀聚合物 8
1-8 生物可分解性高分子 9
1-8-1 聚乳酸種類 10
1-8-2 聚乳酸與甘醇酸性質 10
1-9 抗癌藥物薑黃素 (Curcumin) 13
1-10 研究動機 14
第二章 實驗材料與方法 16
2-1 實驗儀器 16
2-2 實驗藥品 17
2-3 實驗流程 18
2-4製備兩性共聚物 19
2-4-1製備樹枝狀聚胺基甲酸酯(PUAD)高分子 19
2-4-2製備PUAD-PLGA 35
2-5高分子分析與鑑定 36
2-5-1 傅立葉紅外線光譜儀(FT-IR)結構分析 36
2-5-2 核磁共振光譜儀 (1H-NMR) 分析 37
2-6粒徑分析 37
2-7表面電位分析 39
2-8電子顯微鏡照影(TEM) 40
2-9微胞包覆藥物效率 40
2-9-1濃度校正曲線 40
2-9-2包覆藥物效率 41
2-10兩性共聚物載藥UV分析 42
2-11細胞毒性分析 43
2-11-1細胞種類 43
2-11-2配製培養液 43
2-11-3解凍細胞 44
2-11-4細胞培養與繼代 44
2-11-5細胞毒性分析原理 45
2-11-6兩性共聚物對細胞毒性分析 45
2-11-7兩性共聚物包覆Curcumin與Free curcumin對細胞毒性分析 46
2-12微胞之curcumin釋控分析 47
第三章 結果 48
3-1 兩性共聚物結構鑑定與分析 48
3-1-1 G0.5 PUAD、G1.5 PUAD、G2.5 PUAD FT-IR光譜鑑定 48
3-1-2 G1.0 PUAD、G2.0 PUAD、G3.0 PUAD FT-IR光譜鑑定 48
3-1-3 G 2.0 PUAD-EA、G 3.0 PUAD-EA FT-IR光譜鑑定 48
3-1-4 G 2.0 PUAD-NH2、G 3.0 PUAD-NH2 FT-IR光譜鑑定 48
3-1-5 G2.0 PUAD-PLGA、G3.0 PUAD-PLGA FT-IR光譜鑑定 49
3-1-6 G2.0 PUAD-PLGA、G3.0 PUAD-PLGA 1H-NMR光譜鑑定 49
3-2 G2.0 PUAD-PLGA、G3.0 PUAD-PLGA形成微胞之粒徑大小與電位分析 49
3-2-1 PUAD-PLGA微胞備製 49
3-2-2 微胞之粒徑大小 50
3-2-3 微胞之表面電位分析 50
3-2-4 G2.0 PUAD-PLGA、G3.0 PUAD-PLGA之電子顯微鏡分析 50
3-3 藥物包覆效率 51
3-4對COS-7細胞毒性測試 51
3-5對HeLa細胞毒性測試 52
3-6微胞之 curcumin 釋控分析 52
第四章 討論 54
4-1兩性共聚物結構鑑定與分析 54
4-2微胞之粒徑大小與表面電位 55
4-3藥物包覆效率 56
4-4細胞毒性測試 56
4-5藥物釋控分析 57
第五章 結論 59
參考文獻 61
圖與表 68

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