https://scholars.lib.ntu.edu.tw/handle/123456789/83296
標題: | 大腸標的藥物制放:酸鹼敏感性高分子薄膜應用於5-FU制放及其對Caco-2細胞的影響 | 作者: | 王正一 | 關鍵字: | 高分子薄膜;大腸藥物制放;5-FU;Polymer membrane;colon-specific drug delivery | 公開日期: | 31-七月-2002 | 出版社: | 臺北市:國立臺灣大學醫學工程學研究所 | 摘要: | 惡性腫瘤近幾年來一直是台灣地區十 大死因的首位,值得注意的是大腸癌排名 第三名且有逐年增加的趨勢。目前在臨床 上治療大腸癌最有用的藥物為5-FU,但是 傳統治療上經由靜脈注射或點滴注射給藥 大部分會經由肝臟代謝(約80-90%),導致 5-FU 在人體的半衰期只有10-15 分鐘,且 在代謝過程中,5-FU 易對細胞及組織產生 毒性及副作用。 本研究利用乙烯-乙烯醇共聚合物摻入 少量的聚丙烯酸於不同溫度製成薄膜,在 酸性環境中不帶電;而到了微鹼性的環境 則解離帶負電,並因靜電斥力而使薄膜擴 張、孔洞放大,助於藥物的釋放,應用於 大腸標的藥物制放,以提高5-FU 生物可 用率及降低副作用。由膨潤度及5-FU 藥 物制放結果發現,成膜溫度為60℃時,乙 烯-乙烯醇共聚合物poly(ethylene-co-vinyl alcohol) (EVAL)摻入不同比例的聚丙烯酸 poly(acrylic acid) (PAA),能使原本不具有 酸鹼敏感性的乙烯-乙烯醇共聚合物薄膜 具有酸鹼敏感的特性,此特性隨著摻入聚 丙烯酸的量而愈益明顯。成膜溫度為45℃ 及25℃時,因為薄膜的孔洞大,以致於靜 電排斥力的效應降低,酸鹼敏感的特性漸 漸消失。培養Caco-2 細胞可以發現隨著 5-FU 濃度增加細胞活性降低。成膜溫度 60℃的乙烯-乙烯醇共聚合物/聚丙烯酸薄 膜適合發展為大腸標的藥物制放之薄膜。 Recently, malignancy is the leading cause of mortality in Taiwan, and colon cancer accounted approximately 3000 deaths each year. In the recent decade, the most useful drug for therapy of colon cancer is 5-Fluorouracil (5-FU). It has been reported to have considerable toxicity and side effects administered by intravenous injections or via alimentary treat and would be metabolized by liver that result in the half-life only 10~15 minutes in human. Thus, it would be clinically beneficial to localize 5-FU to a particular site within the gastrointestinal tract, either to maximize the therapeutic response to the colon, or to reduce the side effects caused by drug delivered to an inopportune region other than target site. In this study, pH-sensitive polymers with the capability of selectively releasing drug in desired compartment for colon-specific drug delivery was prepared by PAA/EVAL blends. The swelling degree and the 5-FU permeation of PAA/EVAL membranes prepared at 60℃ are functioning as protective carriers of drugs in the pH 2.0. The 5-FU permeation at pH 2.0 was small, which indicates that drugs are protected in the acidic environment. But the pH-sensitive character disappeared gradually at 45℃ and 25℃ of membrane preparation, because the effect of pore size is more than electrical repulsion between adjacent carboxylate ions. This suggests the PAA/EVAL membrane prepared at 60℃ is a potential material for the specific delivery of drugs to the colon for local treatment. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/22357 | 其他識別: | 902213E002074 | Rights: | 國立臺灣大學醫學工程學研究所 |
顯示於: | 醫學工程學研究所 |
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