研究生: |
沙彥彣 |
---|---|
論文名稱: |
抗癌藥物camptothecin與脂質在單分子層及微脂粒中之交互作用情形之研究 |
指導教授: |
朱一民
|
口試委員: | |
學位類別: |
碩士 Master |
系所名稱: |
工學院 - 化學工程學系 Department of Chemical Engineering |
論文出版年: | 2003 |
畢業學年度: | 91 |
語文別: | 中文 |
論文頁數: | 90 |
中文關鍵詞: | camptothecin 、單分子層 、微脂粒 |
相關次數: | 點閱:3 下載:0 |
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低水溶性之抗癌藥物camptothecin (CPT)在人體血液之pH值及血液中血清白蛋白的存在下,易轉化成抗癌活性較小但細胞毒性大的carboxylate結構,造成嚴重之副作用,使臨床應用上效果不佳,因此考慮以微脂粒為藥物載體,避免CPT在人體生理條件下水解以及在血液中與血清白蛋白結合。本研究利用以egg yolk phosphatidylcholine (EPC)及 hydrogenated soybean phosphatidylcholine (HSPC)組成微脂粒為藥物載體包覆CPT,並添加膽固醇及雙十六碳鏈磷酸鹽(dicetyl phosphate,DCP),以期增加微脂粒之穩定度及包覆藥物之效率。
在實際以微脂粒包覆CPT之前,為瞭解脂質與CPT間的交互作用,本研究利用Langmuir trough之單分子層實驗,量測不同莫耳比之HSPC/DCP、DCP/CPT、EPC/DCP、DCP/CPT、HSPC/CPT及EPC/CPT混合單分子層於37℃磷酸緩衝溶液(pH = 7.4)/空氣界面上之界面性質。從過剩自由能之分析,HSPC/DCP 100/80 (莫耳/莫耳)及EPC/DCP 100/40 (莫耳/莫耳) 分別為HSPC/DCP、EPC/DCP系統最穩定之組成比例。此外,原本未有明顯界面性質之CPT,會與DCP、HSPC、EPC作用而改變脂質之界面行為,尤其與DCP間之交互作用最為明顯,由□-A等溫線圖發現,CPT與DCP可以等莫耳比形成混合單分子層,而與EPC或HSPC則最多僅能形成莫耳比EPC/CPT 100/8.8及HSPC/CPT 100/4.4之混合單分子層。
在微脂粒研究中,微脂粒組成為EPC/DCP 100/40 (莫耳/莫耳),可包覆CPT高達CPT/ EPC 8.8/100 (莫耳/莫耳),為包覆藥物量最高之配方。此外本研究在37℃下分別對EPC/DCP 100/40 (莫耳/莫耳) 、EPC/DCP 100/20 (莫耳/莫耳)及HSPC/DCP 100/20 (莫耳/莫耳)三微脂粒系統進行藥物釋放的實驗,結果發現EPC/DCP系統與HSPC/DCP系統之微脂粒有類似之藥物釋放行為。
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