本文選題：膠束 + 攝取與外排��； 參考：《藥學(xué)學(xué)報(bào)》2017年08期

【摘要】：利用小腸上皮細(xì)胞頂膜側(cè)和基底側(cè)pH的差異以及新生兒Fc受體(neonatal Fc receptor,FcRn)與其配體結(jié)合的pH依賴特性可能增加配體修飾的納米載體從小腸上皮細(xì)胞頂膜側(cè)向基底側(cè)的轉(zhuǎn)運(yùn),從而促進(jìn)藥物的吸收。本課題制備了靶向于FcRn的短肽FcBP(IgG Fc段結(jié)合肽,IgG Fc domain-binding peptides)修飾的聚乙二醇-聚ε-己內(nèi)酯[poly(ethyl ethylene phosphate)-co-poly(ε-caprolactone),PEG-PCL]膠束并在人克隆結(jié)腸腺癌細(xì)胞(human colon adenanocaricinoma cell lines,Caco-2)上考察了pH和靶頭密度對膠束攝取與外排過程的影響。采用薄膜水化法制備不同靶頭修飾密度的包載香豆素6(coumarin 6,C6)的PEG-PCL主動(dòng)膠束和被動(dòng)膠束,并用激光粒度測定儀測定其粒徑,透射電鏡觀察其形態(tài),流式細(xì)胞術(shù)測定各主、被動(dòng)膠束在不同pH值下的攝取和外排以及FcRn在膠束攝取中的作用。結(jié)果表明,PEG-PCL膠束的粒徑約為30 nm,FcBP的修飾不影響膠束的粒徑。pH和靶頭密度都對FcBP修飾的PEG-PCL膠束的攝取有影響。主動(dòng)膠束在pH 6.0的攝取量顯著高于在pH7.4的攝取量,并且在兩種pH下主動(dòng)膠束的攝取量都表現(xiàn)出隨靶頭密度的增大先增大后減少的趨勢。進(jìn)一步研究膠束的外排表明,膠束在pH 6.0下攝取后可以在pH 7.4環(huán)境中外排,外排量與靶頭密度有關(guān),其中靶頭密度10%的主動(dòng)膠束外排量最大,顯示出較強(qiáng)的跨膜轉(zhuǎn)運(yùn)遞送的潛力。同時(shí),競爭性抑制實(shí)驗(yàn)驗(yàn)證了膠束的攝取與配體和受體的作用有關(guān)。本研究為應(yīng)用FcBP修飾的PEG-PCL膠束進(jìn)行跨膜轉(zhuǎn)運(yùn)藥物打下一定的基礎(chǔ),為納米載體的設(shè)計(jì)提供了一定的參考。
[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.

【作者單位】： 北京大學(xué)藥學(xué)院;澳門大學(xué)中華醫(yī)藥研究院中藥質(zhì)量研究國家重點(diǎn)實(shí)驗(yàn)室;
【基金】：國家自然科學(xué)基金資助項(xiàng)目(81473159) 國家自然科學(xué)基金-海外及港澳學(xué)者合作研究基金資助項(xiàng)目(81528021)
【分類號】：R943
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本文編號：1745419