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    標題: P醣蛋白運送抗癌藥物之機轉---磷脂質之重要性探討
    Mechanism of Anticancer Drug Transport by P-Glycoprotein---The Possible Role of Phospholipids
    作者: 駱雨利
    Yu-Li Lo
    貢獻者: 藥學系
    關鍵字: P醣蛋白
    磷脂質
    泛愛黴素
    微脂粒
    人類結腸癌細胞

    P-glycoprotein
    Phospholipid
    Epirubicin
    Liposome
    Human colon adenocarcinoma cell
    Intestine
    日期: 1999
    上傳時間: 2008-11-19 15:21:21 (UTC+8)
    出版者: 台南縣:嘉南藥理科技大學藥學系
    摘要: 磷脂質常被用來當作藥物之攜帶體。抗癌藥物若以磷脂質做成之微脂粒包裝,常可降低毒性、增加療效。因此我們研究微脂粒包埋、空的微脂粒或磷脂質對於Epirubicin於人類結腸腺癌細胞(Caco-2)及老鼠小腸之積聚及運送之效應。使用流式細胞分析儀分析,發現微脂粒包埋或空的微脂粒明顯增進Epirubicin於Caco-2細胞之積聚。以Caco-2細胞為模型,發現此二種劑型可顯著促進Epirubicin於吸收方向之運輸及明顯減少Epirubicin於排出方向之運輸。由老鼠小腸之結果發現不管是在空腸或迴腸,此二種劑型均能明顯增進Epirubicin之吸收。實驗結果顯示抑制小腸P醣蛋白或其他排出藥物之蛋白質可能跟Epirubicin之增加吸收及減少排出有關。總結,使用磷脂質做成藥物之微脂粒劑型可以經由抑制P醣蛋白之機轉以促進藥物之小腸吸收,並增進P醣蛋白受質之生體可用率。微脂粒包裝可應用於拮抗癌症化學療法上之多重抗藥性。
    Studies using cancer chemotherapeutic agents such as epirubicin encapsulated in liposomes, made of phospholipids and other ingredients, have generally shown reduced toxicity and enhanced therapeutic efficacy. This study investigated the effects of liposomal encapsulation, empty liposome or free phospholipid addition on the uptake and transport of epirubicin in the human colon adenocarcinoma (Caco-2) cell line and everted gut sacs of rats. The flow cytometric experiments showed that liposomal encapsulation or empty liposome addition significantly increased the intracellular accumulation of epirubicin in CaCo-2 cells. These two formulations substantially enhanced apical to basolateral absorption and significantly reduced the basolateral to apical efflux of epirubicin across Caco-2 monolayers. The epirubicin concentrations measured in everted gut sacs pretreated with these two formulations were significantly higher than those in epirubicin control in both the jejunum and the ileum. The study suggests that inhibition of P-glycoprotein or other transporter proteins located in the intestines may be, at least partially, involved in the reduction of epirubicin efflux. In conclusion, the therapeutic efficacy of epirubicin may be improved by the use of phospholipids as excipients and MDR modulators in the formulations. Liposomal encapsulation may have significant implications in circumventing drug resistance in cancer chemotherapy.
    關聯: 計畫編號:NSC88-2314-B041-009
    顯示於類別:[藥學系(所)] 國科會計畫

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