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自组装混合胶束改善姜黄素口服吸收的机制:体外和体内研究

The mechanism of self-assembled mixed micelles in improving curcumin oral absorption: In vitro and in vivo.

作者信息

Wang Jinling, Ma Wenzhuan, Tu Pengfei

机构信息

Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China.

Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, PR China.

出版信息

Colloids Surf B Biointerfaces. 2015 Sep 1;133:108-19. doi: 10.1016/j.colsurfb.2015.05.056. Epub 2015 Jun 8.

Abstract

Curcumin-loaded self-assembled polymeric micelles (Cur-PMs) were designed to increase oral bioavailability of curcumin and investigate the oral absorption mechanism in vitro and in vivo. The Cur-PMs were spherical nano-size particles 17.82±0.33nm in size, with a drug loading of 3.52±0.18%, and encapsulation efficiency as high as 93.08±2.23%. The intestinal absorption of Cur-PMs in the duodenum, jejunum, and ileum was 3.09-, 6.48-, and 1.78-fold greater than that of curcumin solution (Cur-Sol) at 0.5h. The cellular uptake of Cur-PMs in Caco-2 cells was significantly enhanced in comparison with Cur-Sol by caveolae-mediated and clathrin-mediated endocytosis. Moreover, the apparent permeability coefficient (Papp) of Cur-PMs was 3.50-fold higher than that of Cur-Sol in Caco-2 transport studies. The transport mechanism of Cur-PMs into the system circulation was not paracellular transport through opening the tight junctions, but was by energy-dependent, macropinocytic transcytosis and lymphatic transport pathways. Furthermore, the AUC(0-t) value of Cur-PMs was improved 2.87-fold compared with that of Cur-Sol after oral administration in rats. Therefore, self-assembled polymeric micelles could be a promising vehicle to efficiently improve the oral absorption of curcumin.

摘要

负载姜黄素的自组装聚合物胶束(Cur-PMs)旨在提高姜黄素的口服生物利用度,并在体外和体内研究其口服吸收机制。Cur-PMs为球形纳米颗粒,大小为17.82±0.33nm,载药量为3.52±0.18%,包封率高达93.08±2.23%。在0.5小时时,Cur-PMs在十二指肠、空肠和回肠的肠道吸收分别比姜黄素溶液(Cur-Sol)高3.09倍、6.48倍和1.78倍。与Cur-Sol相比,Cur-PMs在Caco-2细胞中的细胞摄取通过小窝介导和网格蛋白介导的内吞作用显著增强。此外,在Caco-2转运研究中,Cur-PMs的表观渗透系数(Papp)比Cur-Sol高3.50倍。Cur-PMs进入体循环的转运机制不是通过打开紧密连接的细胞旁转运,而是通过能量依赖的巨胞饮转胞吞作用和淋巴转运途径。此外,大鼠口服给药后,Cur-PMs的AUC(0-t)值比Cur-Sol提高了2.87倍。因此,自组装聚合物胶束可能是一种有前途的载体,可有效提高姜黄素的口服吸收。

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