不同疏水结构的两亲性聚合物对MDCK-MDR1细胞P-糖蛋白功能的影响

吴琪, 孙明辉, 赵娟, 李根云, 黄建耿, 李高, 斯陆勤

中国药学杂志 ›› 2018, Vol. 53 ›› Issue (2) : 122-128.

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中国药学杂志
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中国药学杂志 ›› 2018, Vol. 53 ›› Issue (2) : 122-128. DOI: 10.11669/cpj.2018.02.010
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不同疏水结构的两亲性聚合物对MDCK-MDR1细胞P-糖蛋白功能的影响

  • 吴琪1, 孙明辉2, 赵娟1, 李根云1, 黄建耿1, 李高1, 斯陆勤1*
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Effects of Hydrophobic Structure of Amphiphilic Polymers on the Activity of P-glycoprotein in MDCK-MDR1 Cell

  • WU Qi1,SUN Ming-hui2,ZHAO Juan1,LI Gen-yun1, HUANG Jian-geng1,LI Gao1,SI Lu-qin1*
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摘要

目的 研究不同疏水结构的两亲性聚合物单甲醚聚己二醇-聚己内酯聚合物(mPEG-PCL)、单甲醚聚乙二醇-聚D,L-乳酸聚合物(mPEG-PDLLA)、单甲醚聚乙二醇-聚(乳酸-羟基乙酸)聚合物(mPEG-PLGA)对P-糖蛋白(P-glycoprotein,P-gp)外排功能的影响。方法 采用薄膜分散法制备聚合物胶束,动态光散射仪测定胶束粒径,芘荧光探针法测定临界胶束浓度(CMC);以P-gp特异性底物罗丹明123(Rhodamine 123,R123)为荧光探针,采用摄取和外排实验评价聚合物及其形成的胶束对MDCK-MDR1细胞P-gp功能的影响。结果 mPEG-PCL、mPEG-PDLLA、mPEG-PLGA的粒径分别为(55.9±0.2)、(53.7±1.1)和(61.6±0.6)nm;CMC值分别为2.08、5.42和26.4 μg·mL-1;摄取实验结果显示,当mPEG-PCL质量浓度在250 μg·mL-1、mPEG-PDLLA在1~25 μg·mL-1、mPEG-PLGA在1~25 μg·mL-1时,可显著增加细胞内R123累积量,表明三者对P-gp外排功能均有抑制作用;外排实验中mPEG-PCL、mPEG-PDLLA、mPEG-PLGA分别在CMC以上、CMC附近及以下、CMC以下时会显著降低R123外排率,与摄取实验结果相对应。结论 mPEG-PCL、mPEG-PDLLA、mPEG-PLGA聚合物对P-gp外排活性均有一定的抑制作用,其作用程度与疏水段结构、聚合物浓度及存在状态有关。

Abstract

OBJECTIVE To determine the effects of the amphiphilic block polymers,which have the same hydrophilic block with the different hydrophobic block,on the function of P-glycoprotein(P-gp). METHODS The three different micelles were prepared by film dispersion method. The particle sizes and distributions were measured by dynamic light scattering. Critical micelle concentrations(CMC) were detected by fluorescence probe technique with the pyrene. Rhodamine 123,a specific probe substrate of P-gp,was applied to determine the effects of polymers on the function of P-gp using uptake and efflux method. RESULTS The particle sizes of mPEG-PCL、mPEG-PDLLA、mPEG-PLGA were (55.9±0.2),(53.7±1.1) and (61.6±0.6)nm. The CMC values were 2.08, 5.42 and 26.4 μg·mL-1. R123 accumulation in Madin-Darby canine kidney/multidrug resistance 1(MDCK-MDR1)cell detected by uptake assay increased to a maximum in the presence of polymers at concentrations of 250 μg·mL-1 for mPEG-PCL,1~25 μg·mL-1 for mPEG-PDLLA and mPEG-PLGA. In efflux assay, mPEG-PCL、mPEG-PDLLA、mPEG-PLGA decreased the percentage of efflux of R123 at concentrations above the CMC、below/at the CMC or below the CMC respectively,showed the similar RESULTS with uptake assay. CONCLUSION The mPEG-PCL,mPEG-PDLLA,mPEG-PLGA polymers might have a potential to inhibit the efflux activity of P-gp,which was likely related to the structures of hydrophobic segments, concentrations and existing states of the polymers.

关键词

单甲醚聚乙二醇-聚己内酯聚合物 / 单甲醚聚乙二醇-聚D, L-乳酸聚合物 / 单甲醚聚乙二醇-聚乳酸-羟基乙酸聚合物 / P-糖蛋白 / 罗丹明123 / MDCK-MDR1细胞

Key words

mPEG-PCL / mPEG-PDLLA / mPEG-PLGA / P-glycoprotein / Rhodamine 123 / MDCK-MDR1 cells

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吴琪, 孙明辉, 赵娟, 李根云, 黄建耿, 李高, 斯陆勤. 不同疏水结构的两亲性聚合物对MDCK-MDR1细胞P-糖蛋白功能的影响[J]. 中国药学杂志, 2018, 53(2): 122-128 https://doi.org/10.11669/cpj.2018.02.010
WU Qi,SUN Ming-hui,ZHAO Juan,LI Gen-yun, HUANG Jian-geng,LI Gao,SI Lu-qin. Effects of Hydrophobic Structure of Amphiphilic Polymers on the Activity of P-glycoprotein in MDCK-MDR1 Cell[J]. Chinese Pharmaceutical Journal, 2018, 53(2): 122-128 https://doi.org/10.11669/cpj.2018.02.010
中图分类号： R944   

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基金

国家自然科学基金资助项目(81473170)

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