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題名 | Use of Pharmaceutical Excipient Cremophor EL for Enhancing 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 |
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作者 | 駱雨利; 徐筑吟; 黃金鼎; | 書刊名 | 鄭氏藥學文教基金會研究彙刊 |
卷期 | 3:1 1999.03[民88.03] |
頁次 | 頁75-81 |
分類號 | 418.1 |
關鍵詞 | P醣蛋白; 結腸線癌細胞; 賦形劑; 流式細胞分析儀; P-glycoprotein; Caco-2; Epirublcin; Excipients; Flow cytomerty running head: effects of cremophor EL on epirubicin accumulation in caco-2; |
語文 | 英文(English) |
中文摘要 | 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。培養之結腸線癌細胞(Caco-2)已知具小腸細胞之生長形態,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(100 ug/ml)之Cremophor EL較低濃度(10 ug/ml)之Cremophor EL效果好。這個界面活性濟類賦形劑之足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(Caco-2)內之積聚。吏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。 |
英文摘要 | P-glycoprotein (P-gp) reduces the intracellular concentration, and therefore the effectiveness. of anticancer drugs, such as eplrubicin, in the tumor cells. P-gp also expresses in the ssmall intestine at normal physological conditions. Inhibition of intestinal P-gp function using MDR reversing agents may enhance oral bioavailability 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 epirubicn by flow cytometer. The effects of low (10 ug/ml) and high (100 ug/ml) concentrations of Cremophor EL were also compared. Cremophor EL significantly increased intracellular accumulation of epirubicin. 100 ug/ ml Cremophor EL had more enhancing effect than 10 ug/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 achieved in in vlvo situation. Use of surfactants in excipients may increase intestinal absorption of some drugs through the mechanism of P-gp inhibition and thus improve drug bioavailability for P-gp substrates. |
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