本研究利用聚酯類溫度敏感型水膠作為藥物載體，包覆免疫抑制劑環孢靈。希望能藉由藥物控制釋放系統，達到緩慢且持續釋放的效果。材料合成主要是以methoxy poly(ethylene glycol)作為起始劑，與D,L-lactide、Glycolide、δ-Valerolactone進行開環聚合反應，合成出mPEG-PLGA及mPEG-PVLA兩種二團聯共聚物。
合成所得之產物，利用1H-NMR分析其化學結構，經判斷其結構正確無誤，分子量主要由凝膠滲透層析儀(GPC)做分析。其最低臨界溶解溫度(Lower critical solution temperature, LCST)之性質，利用紫外光可見光光度計來做分析，兩種二團聯共聚物其最低臨界溶解溫度(LCST)約為35℃左右。此外也針對其溶膠相轉換(sol-gel phase transition)作測試，以觀察各濃度之成膠溫度以及成膠範圍，結果顯示此兩種水膠成膠溫度均在35℃以下。體外藥物釋放則是利用水膠包覆環孢靈(Cyclosporine A, CyA)藥物，在溫度37oC環境下釋放兩個星期，結果顯示此系統可讓藥物穩定釋放且在一個禮拜之後藥物濃度逐漸呈現平穩的趨勢。
動物體內實驗方面，則是經由皮下注射觀察在體內成膠情形並測試此材料在大鼠體內之相容性，結果顯示水膠可以在注射後立即在注射部位成膠，並維持兩個星期且不會有死亡現象產生。最後利用水膠包覆環孢靈作動物體內藥物釋放。和直接注射藥物比較起來，利用水膠包覆要藥物作釋放能使藥物在體內濃度呈現較平穩的趨勢，並且可以在體內維持比較長的時間。

摘要 Ⅰ
英文摘要 III
目錄 IV
圖目錄 ⅤII
表目錄 IX
第一章 文獻回顧 1
1.1 生醫材料簡介 1
1.2 高分子藥物控制釋放系統 3
1.3 生物可分解高分子藥物載體 6
1.3.1 人工合成高分子 7
1.3.3 影響材料降解之因素 10
1.4 高分子水膠 11
1.4.1 智慧型水膠 14
1.4.2聚乙二醇構成之溫度敏感型水膠 18
1.5 自體免疫 20
1.5.1 免疫耐受性 21
1.5.2 器官移植 22
1.6 免疫抑制劑 23
1.6.1 環孢靈 24
第二章 研究動機與目的 26
第三章 實驗部份 28
3.1 實驗藥品 28
3.2 實驗儀器 29
3.3 實驗流程 30
3.4 實驗步驟 31
3.4.1 二團聯共聚物mPEG-PLGA之合成 31
3.4.2二團聯共聚物mPEG-PVLA之合成 32
3.4.3產物結構分析與性質測定 33
3.4.4體外藥物釋放 35
3.4.4.1單層水膠釋放系統 35
3.4.4.2雙層水膠釋放系統 37
3.4.5 HPLC檢測條件及標準曲線的製作 37
3.4.6高分子水膠在動物體內毒性測試 38
3.4.7高分子水膠含有環孢靈藥在動物體內毒性測試 39
3.4.8水膠在動物體內成膠情形 39
3.4.9動物體內藥物釋放 40
第四章 結果與討論 41
4.1二團聯共聚物合成反應討論 41
4.2 1H-NMR結構鑑定 42
4.3分子量分析 44
4.4臨界微胞濃度 45
4.5微胞粒徑測試 46
4.6最低臨界溶解溫度(LCST)測試 47
4.7溶液膠體相轉換測試 48
4.8體外降解測試 50
4.9體外藥物釋放 52
4.9.1單層水膠釋放系統 52
4.9.2雙層水膠釋放系統 59
4.10材料在動物體內毒性之測試 61
4.11水膠在動物體內成膠情形 63
4.12動物體內藥物釋放 67
第五章 結論與未來展望 68
第六章 參考文獻 70
第七章 附錄 74

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