4种药用辅料在Caco-2细胞模型中对塞利洛尔跨膜转运的影响.docVIP

4种药用辅料在Caco-2细胞模型中对塞利洛尔跨膜转运的影响 黄建耿a，斯陆勤a，范昭泽a，吴祥根a，裘军b，李高a,基金项目 基金项目:国家自然科学基金资助项目；湖北省卫生厅科研基金项目（JX2B04） ?通讯作者:李高,男,博士生导师,教授 Tel（Fax）:（027E-mail:ligaotj@163.com 作者简介:黄建耿,男,博士研究生 （华中科技大学药学院:a.药剂系b.药理系，武汉，430030） 摘要：目的 研究聚乙二醇400、聚氧乙烯蓖麻油、普朗尼克和羟丙基-β-环糊精在Caco-2细胞模型中对塞利洛尔跨膜转运的影响 方法 本实验利用HPLC法测定药物浓度，以塞利洛尔为探针药物，维拉帕米为阳性对照，分别考察了不同条件下，包括变换HBSS溶液pH值、改变药物浓度以及加入4种药用辅料，塞利洛尔在Caco-2细胞单层膜的转运情况。结果 塞利洛尔组AP-BL与BL-AP方向表观渗透系数Papp分别为(0.333±0.018)×10-6cm·s-1和(2.10±0.13)×10-6cm·s-1；随着4种辅料加入浓度的增加，塞利洛尔AP-BL方向Papp增加，BL-AP方向Papp降低。结论 4种药用辅料与维拉帕米通过抑制P-糖蛋白药泵作用，促进塞利洛尔AP-BL方向转运，抑制 关键词：Caco－2细胞模型；P-糖蛋白；聚乙二醇400；聚氧乙烯蓖麻油；普朗尼克；羟丙基-β-环糊精；塞利洛尔 Effect of 4 pharmaceutic excipients on transport of celiprolol across Caco-2 cell monolayer HUANG Jian-genga, SI Lu-qina, FAN Zhao-zea, WU Xiang-gena, QIU Junb, LI Gaoa* (aDepartment of Pharmaceutics, bDepartment of Pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China) ABSTRACT: OBJECTIVE To study the effect of pharmaceutic excipients including PEG 400, Cremophor EL, Pluronic and HP-β-cyclodextrin on celiprolol transepithelial transport with caco-2 cell monolayer model. METHOD The concentration of celiprolol was measured by HPLC and Caco-2 cell monolayer model was established to perform experiments with verapamil set as a positive control. The transportation of celiprolol across the Caco-2 cell monolayer were determined under various conditions, including changing pH of HBSS and celiprolol concentration and adding 4 pharmaceutic excipients affecting absorption. RESULTS The apparent permeability coefficient (Papp) of celiprolol transport from Apical to Basolateral and Basolateral to Apical was (0.333±0.018)×10-6cm·s-1 and (2.101±0.128)×10-6cm·s-1, respectively. With the increasing of 4 pharmaceutic excipient concentration, Papp of celiprolol transport from Apical to Basolateral increased and that from Basolateral to Apical decreased. CONCLUSION 4 Pharmaceutic adjuvants and verapamil can enhance celip