溫度敏感型胺基酸水膠成膠機制探討 與親水性抗癌藥物投遞之應用

Gelation studies and Hydrophilic Anti-Cancer Drug Delivery by Thermosensitive Polypeptide Hydrogel

洪唯倫(Wei-Lun Hung)

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

本研究探討可應用於原位成膠，長效釋放抗癌藥物的溫度敏感型水膠劑型。
有潛力用於乳癌術後化療，防止原位復發等應用。本研究合成之溫度敏感型胺基
酸水膠高分子為甲基化聚乙二醇- 左旋聚丙胺酸(methoxy-poly(ethylene
glycol)-polyalanine, mPEG-L-PA)。以1H 與13C 核磁共振光譜儀、傅立葉轉換反
射式紅外線光譜儀、凝膠滲透層析儀、流變儀、圓二色光譜儀、掃描式電子顯微
鏡與穿透式電子顯微鏡分析建立胺基酸水膠mPEG-Alanine 膠體性質與成膠機制。
水膠胺基酸所接鏈段越長其成膠溫度越低，黏度與彈性體性質越佳。由CD 與
ATR-FTIR 分析可發現在低濃度環境下，mPEG-Alanine 二級結構隨著溫度上升
逐漸減少。而在ATR-FTIR 分析高濃度水膠樣品二級結構，隨著溫度上升，β-sheet
結構也隨之增加。在藥物包覆與釋放方面，選擇親水性抗癌藥物：5-氟尿嘧啶，
將其包覆於水膠後於磷酸鹽緩衝溶液(pH = 7.4)，以高效能液相層析儀探討藥物
釋放情形：相同水膠材料包覆不同5-氟尿嘧啶藥量藥物釋放；不同Alanine 鏈段
長度mPEG-Alanine 水膠包覆相同5-氟尿嘧啶藥量與彈性蛋白酶存在與否對於藥
物釋放作一比較。mPEG-Alanine 結構穩定度相當良好，經Elastase 酵素作用十
天只降解約百分之二十。在藥物釋放方面，其釋放量約百分之三十五至百分之六
十，顯示藥物包覆情況良好。

關鍵字

溫度敏感型胺基酸水膠 ； 5-氟尿嘧啶 ； 原位成膠

並列摘要

We synthesized a series of mPEG-L-PA diblock copolymers and investigated the
hydrophobic block length effect on the secondary structure influencing the
nanostructure of the self-assembled amphiphilic copolymers, the thermosensitivity of
the hydrogels in aqueous solution.
Poly(ethylene glycol) methyl ether-peptide (mPEG-peptide) hydrogels consist of
a mPEG and peptide block, both of which have been shown to exhibit excellent cell
compatibility and low toxicity alone and as a block copolymer. Taken together,
thermosensitive mPEG-peptide hydrogels are attractive candidates for drug delivery
applications.
In this study, we propose the use of a thermosensitive mPEG-peptide hydrogel
for drug delivery with encapsulating 5-Fluorouracil (5-FU). Incorporation and release
of these molecules will be evaluated in vitro as proof of concept for drug
encapsulation. Future work will involve the injection of hydrogel for the evaluation of
toxicity and compatibility.

並列關鍵字

thermosensitive polypeptide hydrogel ； 5-fluorouracil ； in-situ gelation

參考文獻

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