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    標題: Use of Pharmaceutical EXCIPIENT Cremophor EL of Enhnancing Intracellular Accumulation of Epirubicin in Caco-2 Cell Line
    使用賦形劑當作多重抗藥性抑制劑以促進抗癌藥物Epirubicin於結腸腺癌細胞(Caco-2)內之積聚
    作者: 駱雨利
    徐筑吟
    黃金鼎
    貢獻者: 藥學系
    關鍵字: P-glycoprotein
    Caco-2
    epirubicin
    excipients
    flow cytometry Runnlng head: effects of Cremophor EL.on epirubicin accumulation In Caco-2p
    醣蛋白
    結腸腺癌細胞
    Epirubicin
    賦形劑
    流式細胞分析儀
    日期: 1997
    上傳時間: 2010-08-11 11:28:44 (UTC+8)
    摘要: P-glycoprotein (P-gp) reduces the intracellular concentration, and therefore the effectiveness, of anticancer drugs, such as epirubicin, in the tumor cells. P-gp also expresses in the small intestine at normal physiological conditions. Inhibition of intestinal P-gp function using MDR.eversing agents may enhance oral bioavallability of some chemotherapeutic agents. Human colon adenocarcinoma (Caco-2) cell line expresses many characteristics of differentiated cells of the normal small intestine. Using Caco-2 as an in vitro intestinal model, the overall goal of the present study is to evaluate the MDR reversing effects of one commonly used nonabsorptive pharmaceutical excipient, Cremophor EL on the intracellular accrmulation of epirublicn by flow cytometer.The effects of low (10μg/ml) and high (100 μg/ml) concentrations of Cremophor EL were also compared. Cremophor EL significantly increased intracellular accumulation of epirubicin. 100μg/ml Cremophor EL had more enhancing effect than 10μg/ml of the same material. The enhancing effect of Cremophor EL was better than that of non-surfactant MDR reversing agents such as dipyridamole and quinidine. In conclusion, our results demonstrate that Cremophor EL is a potent MDR modifier of epirubicin in Caco-2 at concentrations that could be achlieved in in vivo situation. Use of surfactants in exciplients may increase intestinal absorption or some drugs through the mechanism of P-gp inhibition and thus improve drug bioavailability for P-gp substrates.
    P醣蛋白可排出許多抗癌藥物,因此降低抗癌藥物例如Epirubicin之療效。在正常生理情況下,P醣蛋白於小腸亦有表現。如能使用多重抗藥物抑制劑以抑制小腸P醣蛋白之功能,將有助於促進化學療劑之生體可用率。培養之結腸腺癌細胞(Caco-2)已知具小腸細胞之生長型態,並會表現P醣蛋白。因此本研究使用Caco-2模擬體外小腸模型,以流式細胞分析儀評估常用之非吸收性賦形劑Cremophor EL當作多重抗藥性抑制劑時對Epirubicin於細胞內積聚之影響。Cremophor EL明顯增進Epirubicin於癌細胞之積聚。高濃度(100μg /ml)之Cremophor EL較低濃度(10μg /ml)之Cremophor EL效果好。這個界面活性劑類賦形劑之促進效果明顯地較非界面活性劑類藥物Dipyridamole和Quinidine為佳。總結,實驗結果顯示Cremophor EL為有效之多重抗藥性抑制劑,能以體內試驗可用之濃度以促進抗癌藥物Epirubicin於結腸線癌細胞(Cac0-2)內之積聚。使用界面活性劑於賦形劑中可以經由抑制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。
    關聯: 嘉南學報 23期: p.18-24
    顯示於類別:[嘉南學報] 23期 (1997)
    [藥學系(所)] 期刊論文

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