利用溫度敏感型胺基酸水膠包覆抗癌藥物於控制釋放之研究

Control release of anticancer drug on degradable polypeptide mPEG-PELG hydrogel

周領偉(Chou, Ling Wei)

指導教授 ： 朱一民

國立清華大學/工學院/化學工程學系/碩士(2015年)

摘要

本研究主要探討利用溫度敏感性型水膠：甲基化聚乙二醇-聚乙基左旋穀氨酸(mPEG-PELG)包覆抗癌藥物薑黃素，並達到長期藥物釋放之效果。透過mPEG-NH2對環化穀氨酸(glutamate-NCA)做開環聚合反應，合成出不同親疏水比例的水膠分子。水膠相轉換測試可知隨著疏水端越長，同一濃度下的成膠溫度越低。藉由流變儀觀察機械性質會隨著溫度變化而改變，表示此水膠具有溫度敏感性。再者由圓二色光譜、ATR-FTIR、13C-NMR、CMC測定和TEM圖則可說明，水膠分子形成膠體態的成膠機制。透過Live/dead stain和MTT assay可說明水膠有良好的生物相容性，水膠的重量損失則顯示胺基酸水膠需透過酵素來降解，包覆抗癌藥物薑黃素的結果也說明了能達到持續的藥物釋放，同時釋放的薑黃素仍可抑制癌細胞的生長。針對這些結果，mPEG-PELG溫感型胺基酸水膠於藥物釋放領域上有相當的應用潛力。

關鍵字

溫感性胺基酸水膠 ； 薑黃素 ； 藥物釋放

並列摘要

The objective of this study is to discuss the thermosensitive hydrogel based on mPEG poly(L-glutamate)s sustain delivery of anticancer drug. A series of amphiphilic diblock copolymer were synthesized by ring-opening polymerization (ROP) of γ-ethyl-L-glutamate N-carboxyanhydrides, using mPEG-NH2 as macroinitiator. The copolymer were characterized by 1H-NMR, ATR-FTIR and determined successfully synthesized. Through temperature changed in response to observe material diversification, we could know the polypeptides containing more ethyl groups showed significantly low critical gelation temperatures (CGTs). Circular dichroism (CD), ATR-FTIR, 13C-NMR, CMC and TEM results indicated that the mechanism of the hydrogel formation. Live/dead and MTT assay studies suggested acceptable biocompatibility of our materials in vitro and the mass loss of hydrogel was accelerated in presence of elastase. Moreover, the gel was tried as injectable implants to encapsulate anticancer drug, curcumin(CUR), and the results demonstrated that the CUR-incorporated hydrogel could efficiently inhibit the tumor cell growth. We believed the thermosenstive polypeptide hydrogels has potential for biomedical applications due to its
good biodegradability, biocompatibility, and in situ gelation behavior.

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