傳統上，PLGA作為藥物載體大多應用於長效釋放，其釋放機制主要為PLGA微粒水解後的藥物釋放。然而在癌症的治療上，常常需要於短時間快速大量的釋放抗癌藥物於癌症患部，使癌細胞大量快速死亡，故傳統劑型無法達此要求。本研究提出一可快速釋放的藥物載體系統。我們將PLGA利用雙乳化製備方法包覆碳酸氫鈉和抗癌藥物Doxorubicin，利用碳酸氫鈉對於酸性環境會產生二氧化碳的特性，在endosome內產生二氧化碳來破壞殼層結構並釋放抗癌藥物Doxorubicin，作為能在短時間內釋放的劑型。實驗分為三大部分，第一部分為利用雙乳化製備方法，製備出PLGA微粒，探討不同碳酸氫鈉比例對於PLGA微粒型態的影響，找出最適化的製備參數。第二部分則是檢驗包覆碳酸氫鈉的PLGA微粒放置於不同酸性環境下，探討Doxorubicin的釋放曲線；同時也利用場發式掃描式電子顯微鏡觀察PLGA微粒表面型態的改變。第三部份是將人類肝癌細胞(Hep 3B)作為細胞測試的模型，將PLGA微粒與細胞共培養後，利用共軛焦螢光顯微鏡來觀察細胞核是否會呈現紅色螢光以驗證Doxorubicin的釋放。此外也利用細胞活性測試(MTT Assay)來驗證PLGA微粒具有毒殺肝癌細胞的能力。由以上三部分的實驗可驗證我們所製備的PLGA微粒具有攜帶藥物與毒殺肝癌細胞的能力，而釋放時間也比傳統PLGA微粒來的快，因此具備作為短時間釋放劑型的潛力。

第一章 緒論............................................ 1
1.1 藥物制放系統....................................... 1
1.2 癌症............................................... 2
1.3 生物可降解性高分子材料............................. 3
1.4 碳酸氫鈉(Sodium Bicarbonate)....................... 5
1.5 小紅莓(Doxorubicin)................................ 6
1.6 乳化系統的製備方法................................. 7
1.7 研究目的與動機..................................... 10

第二章 PLGA微粒材料性質分析............................ 13
2.1 研究目的........................................... 13
2.2 利用雙乳化方法製備不同比例碳酸氫鈉的PLGA微粒....... 13
2.3 繞射分析(X-ray Diffraction)........................ 15
2.4 場發式掃描式電子顯微鏡(Field-Emission SEM)......... 17
2.5 螢光光譜儀(Fluorescence spectrophotometer)......... 20
2.6 碳酸氫鈉產生二氧化碳起泡測試....................... 23
2.7 利用場發式掃描式電子顯微鏡觀察PLGA微粒的表面型態... 23
2.8 實驗結果與討論..................................... 23

第三章 PLGA微粒酸鹼性質測試............................ 28
3.1 研究目的........................................... 28
3.2 包覆不同碳酸氫鈉PLGA微粒於不同酸鹼環境Doxorubicin的釋放 曲線................................................... 28
3.3 利用場發式掃描式電子顯微鏡觀察放入不同酸鹼環境下PLGA微粒的表面型態改變......................................... 29
3.4 實驗結果與討論..................................... 30

第四章 利用Hep 3B細胞株將PLGA微粒作為治療肝癌的藥物釋放載體..................................................... 35
4.1 研究目的........................................... 35
4.2 細胞培養........................................... 35
4.3 細胞存活率測試(MTT Assay).......................... 35
4.4 利用共軛焦螢光顯微鏡(Confocal Laser Microscope)觀察包覆不同比例碳酸氫鈉PLGA微粒釋放Doxorubicin的情況.......... 37
4.5 實驗結果與討論..................................... 38

Reference.............................................. 42

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