研究生: |
徐齊澤 CHI-TSE, HSU |
---|---|
論文名稱: |
以聚醚胺改質雙馬來醯亞胺/N,N’-二丁基巴比妥酸藥物傳遞之應用 N,N’-Bismaleimide-4,4-diphenylmethane / N,N’-Dibutylbarbituric Acid modified by Jeffamine for Drug Delivery |
指導教授: |
陳崇賢
Chorng-Shyan Chern |
口試委員: |
邱信程
Hsin-Cheng Chiu 鄭智嘉 Chih-Chia Cheng |
學位類別: |
碩士 Master |
系所名稱: |
工程學院 - 化學工程系 Department of Chemical Engineering |
論文出版年: | 2019 |
畢業學年度: | 108 |
語文別: | 中文 |
論文頁數: | 71 |
中文關鍵詞: | 聚醚胺 、雙馬來醯亞胺 、N,N’ -二丁基 巴比妥酸 、巴比妥酸 、藥物傳遞 |
外文關鍵詞: | Jeffamine (M-1000), N,N’ -Bismaleimide-4,4-diphenylmethane, N,N’ - Dibutylbarbituric Acid, barbituric Acid, Drug Delivery |
相關次數: | 點閱:626 下載:0 |
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本研究以雙馬來醯亞胺
(N,N ´ bismaleimide 4,4 ´ diphenylmethane, BMI) 與
N,N ´ 二丁基巴比妥酸 (N,N ´ Dibutylbarbituric Acid, DBB) 調整 B MI/ DBB 莫爾比
為 2/1 及 3/1 進行聚合反應 ,再使用 Jeffamine M 100 0 進行改質,分別添加
20%JF 、 30%JF 及 50%JF ,最後形成親水性之 BMI/DBB JF 樣品。
因本研究所合成之
BMI/DBB JF 具 有酸鹼應答性,其在低 pH 值時, JF
因而質子化,排斥力上升 使 粒徑上升;在高 pH 值時, JF 的立體障礙使粒徑
維持不變,故樣品包覆 DOX 後於低 pH 值時會因膨潤與質子化,而 釋放較多比
例之 DOX 藥物。
以
HeLa 細胞測試未包覆 DOX 之樣品,發現樣品 皆無明顯之細胞毒性;但
若將樣品包覆 DOX 則在高濃度下有明顯的細胞毒性,證明具有毒殺癌細胞的
功用。
另外於細胞吞噬實驗則能進一步了解包覆
DOX 之樣品因靜電作用力而吸
附於細胞周圍,並釋放 DOX 進入細胞核 故確定此一載體具有酸鹼應答性且
有應用在藥物載體之潛力。
In this study, we synthesis BMI/DBB hydrogel by N,N´ -bismaleimide-4,4´ -diphenylmethane (BMI) and N,N´-Dibutylbarbituric Acid (DBB), then graft with Jeffamine M-1000 (JF) to provide pH sensitive hydrogel.
In low pH, hydrogel swells as NH group of JF protonates, so the repulsive force is stronger. In contrast, in higher pH, diameter of hydrogel remains the same because of the steric hindrance of JF. Because of swelling and protonation in low pH, drug release percentage is higher than high pH.
There is no toxicity of BMI/DBB – JF hydrogel with Hela cell, but it has pronounced toxicity with Doxorubicin (DOX)loaded hydrogel.
The Cell uptake assay provides the mechanism of DOX loaded hydrogel with Hela cell, hydrogel adsorbs on the cell because of electrostatic attraction, and it releases DOX into nucleus to affect the Hela cell. According to experimental research, this pH sensitive hydrogel has the potential to be used in medical carrier field.
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