高分子薄膜及奈米粒子於藥物傳輸之應用

Application of polymeric membranes and nanoparticles on drug delivery

賴秉杉(Ping-Shan Lai)

指導教授 ： 王正一

共同指導教授 ： 謝銘鈞

國立臺灣大學/工學院/醫學工程學研究所/博士(2006年)

https://doi.org/10.6342/NTU.2006.00881

摘要

藥物傳輸系統的開發與設計一直以來都是相當熱門的課題，除了利用高分子作為藥物包覆材料外，近年來奈米藥物載體也逐漸受到重視。
本論文分為兩部分，第一部份是利用高分子薄膜技術發展大腸藥物釋放系統，以解決大腸標的給藥的臨床問題。此部分分為兩個研究主題：1. 利用化學修飾技術將甘胺酸接枝於聚乙烯乙烯醇薄膜上，2. 將聚丙烯酸與聚乙烯乙烯醇摻合後製膜，使其具有酸鹼敏感特性，以利大腸藥物釋放。
第二部分是利用樹枝狀高分子作為藥物載體，結合光化學內化技術達到藥物傳輸的目的。此部分同樣分為兩個研究主題：1. 將毒素(saporin)與樹枝狀高分子鍵結，並合併光化學內化(photochemical internalization)技術探討毒素進入癌細胞的情形及毒殺效果。2. 將化療藥物小紅莓(doxorubicin)利用不同鍵結接至樹枝狀高分子表面，並探討不同光化學內化技術對於藥物釋放及細胞毒性的影響。
本研究成功地開發出具酸鹼敏感性的聚乙烯乙烯醇薄膜，並適合用於大腸標的給藥；此外，我們也利用奈米高分子鍵結及光化學內化技術，成功地將不易進入細胞的毒素變成大量進入細胞，並具有良好的細胞毒殺效果；同時我們也發現如果利用酸鹼敏感性的鍵結進行藥物釋放，在合併「後」光化學內化技術能有較好的細胞毒殺效果。
綜上所述，本研究成果將有助於開發大腸藥物給藥系統及奈米光化學給藥技術，期望未來能應用於在臨床醫學上。

關鍵字

大腸藥物傳輸 ； 高分子薄膜 ； 酸鹼敏感性 ； 樹枝狀高分子 ； 光化學內化

並列摘要

In recent years, there has been a rapid growth in the area of drug delivery, facilitated by novel technologies such as smart polymer and nanotechnology that has become a promising field in pharmaceutical sciences.
This dissertation was divided into two parts. The first part is to develop the polymeric membranes for colonic drug delivery to resolve the difficulties of clinical treatment. There are two topics of research in this part. The first topic is to prepare the pH-sensitive membrane for colon-specific drug delivery via glycine-immobilized poly(ethylene-co-vinyl alcohol) (EVAL) membrane. Another topic is to blend the EVAL with poly(acrylic aicd) for colonic drug release.
The second part of the dissertation is to investigate the drug delivery systems of nanocarriers combined with photochemical internalization (PCI). This part also contains two topics of research. The first topic is to develop the toxin delivery system by the dendrimer conjugation and PCI treatment. The second one is to investigate the effects of the linkage between dendrimer and doxorubicin combined with PCI strategies on drug release and cytotoxicity.
In this study, the pH-sensitive polymeric membranes were successfully prepared for colonic drug delivery. Moreover, the cell uptake and cytotoxicity of saporin were improved significantly by dendrimer conjugation combined with PCI technology. We also found out the ‘light after’ PCI treatment was more efficient than the ‘light before’ PCI treatment in releasing DOX from the pH-cleavable conjugates, resulted in more nuclear accumulation of DOX and more cell death after treatment.
In summary, the results were very helpful for the development of colonic drug delivery system and nano-photochemical-induced drug delivery in clinical treatment.

並列關鍵字

Colonic drug delivery ； polymeric membrane ； pH-sensitive ； dendrimer ； photochemical internalization

參考文獻

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