pH和靶头密度对FcBP修饰的PEG-PCL胶束在Caco-2细胞上摄取与外排的影响

发布时间：2018-04-13 17:07

  本文选题：胶束 + 摄取与外排　； 参考：《药学学报》2017年08期

【摘要】：利用小肠上皮细胞顶膜侧和基底侧pH的差异以及新生儿Fc受体(neonatal Fc receptor,FcRn)与其配体结合的pH依赖特性可能增加配体修饰的纳米载体从小肠上皮细胞顶膜侧向基底侧的转运,从而促进药物的吸收。本课题制备了靶向于FcRn的短肽FcBP(IgG Fc段结合肽,IgG Fc domain-binding peptides)修饰的聚乙二醇-聚ε-己内酯[poly(ethyl ethylene phosphate)-co-poly(ε-caprolactone),PEG-PCL]胶束并在人克隆结肠腺癌细胞(human colon adenanocaricinoma cell lines,Caco-2)上考察了pH和靶头密度对胶束摄取与外排过程的影响。采用薄膜水化法制备不同靶头修饰密度的包载香豆素6(coumarin 6,C6)的PEG-PCL主动胶束和被动胶束,并用激光粒度测定仪测定其粒径,透射电镜观察其形态,流式细胞术测定各主、被动胶束在不同pH值下的摄取和外排以及FcRn在胶束摄取中的作用。结果表明,PEG-PCL胶束的粒径约为30 nm,FcBP的修饰不影响胶束的粒径。pH和靶头密度都对FcBP修饰的PEG-PCL胶束的摄取有影响。主动胶束在pH 6.0的摄取量显著高于在pH7.4的摄取量,并且在两种pH下主动胶束的摄取量都表现出随靶头密度的增大先增大后减少的趋势。进一步研究胶束的外排表明,胶束在pH 6.0下摄取后可以在pH 7.4环境中外排,外排量与靶头密度有关,其中靶头密度10%的主动胶束外排量最大,显示出较强的跨膜转运递送的潜力。同时,竞争性抑制实验验证了胶束的摄取与配体和受体的作用有关。本研究为应用FcBP修饰的PEG-PCL胶束进行跨膜转运药物打下一定的基础,为纳米载体的设计提供了一定的参考。
[Abstract]:By using the difference of intestinal epithelial cell apical membrane and basolateral side of pH and the neonatal Fc receptor (neonatal Fc, receptor, FcRn) and its ligand pH may increase the dependence of nano carrier ligand modified from intestinal epithelial cell apical membrane lateral basolateral transport, thereby promoting drug absorption. The preparation of targeted FcRn FcBP (IgG peptide Fc binding peptide, IgG Fc domain-binding peptides) modified polyethylene glycol [poly polycaprolactone (ethyl ethylene phosphate) -co-poly (-caprolactone), PEG-PCL] in micelles and cloning of human colon cancer cells (human colon adenanocaricinoma cell lines, Caco-2) on the effects of pH and the target density on micellar uptake and efflux process. Different targetedpp density package Zaixiang coumarin 6 by thin film hydration method (coumarin 6, C6) PEG-PCL active and passive micelle micelles, and laser Size determination of the particle size were observed by transmission electron microscope, the determination of the main flow cytometry. The effect of passive micelles at different pH values of the uptake and efflux and uptake of FcRn in micelles. The results showed that the PEG-PCL micelle diameter was about 30 nm. The effect of FcBP modification does not affect the glue beam diameter.PH and the target density of PEG-PCL micelle modified FcBP uptake of micelles in the amount of 6. The active uptake of pH was significantly higher than that in the uptake of pH7.4, and the uptake of pH in the two active micelles showed the trend of first increases with the target density after reduced further. Study on the efflux of micelles showed that the micelle can be in pH 7.4 efflux under pH 6 uptake after discharge is related to the target density, the target density of 10% active micelle displacement, showed strong transmembrane delivery potential. At the same time, the real competitive inhibition It is verified that the uptake of micelles is related to the roles of ligands and receptors. This study lays a foundation for transmembrane transport of PEG-PCL micelles modified by FcBP, providing a reference for the design of nano carriers.

【作者单位】： 北京大学药学院;澳门大学中华医药研究院中药质量研究国家重点实验室;
【基金】：国家自然科学基金资助项目(81473159) 国家自然科学基金-海外及港澳学者合作研究基金资助项目(81528021)
【分类号】：R943
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本文编号：1745419