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通过Soluplus/泊洛沙姆F127二元混合胶束系统提高芹菜素的溶解度和口服生物利用度。

Improved solubility and oral bioavailability of apigenin via Soluplus/Pluronic F127 binary mixed micelles system.

作者信息

Zhang Zhenhai, Cui Changchang, Wei Fang, Lv Huixia

机构信息

a Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Chinese Medicine , Nanjing , PR China.

b Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing , PR China.

出版信息

Drug Dev Ind Pharm. 2017 Aug;43(8):1276-1282. doi: 10.1080/03639045.2017.1313857. Epub 2017 Apr 18.

Abstract

The aim of this study was to develop a novel mix micelles system composing of two biocompatible copolymers of Soluplus and Pluronic F127 to improve the solubility, oral bioavailability of insoluble drug apigenin (AP) as model drug. The AP-loaded mixed micelles (AP-M) were prepared by ethanol thin-film hydration method. The formed optimal formulation of AP-M were provided with small size (178.5 nm) and spherical shape at ratio of 4:1 (Soluplus:Pluronic F127), as well as increasing solubility of to 5.61 mg/mL in water which was about 3442-fold compared to that of free AP. The entrapment efficiency and drug loading of AP-M were 95.72 and 5.32%, respectively, and a sustained release of AP-M was obtained as in vitro release study indicated. Transcellular transport study showed that the cell uptake of AP was increased in Caco-2 cell transport models. The oral bioavailability of AP-M was 4.03-fold of free AP in SD rats, indicating the mixed micelles of Soluplus and Pluronic F127 is an industrially feasible drug delivery system to promote insoluble drug oral absorption in the gastrointestinal tract.

摘要

本研究的目的是开发一种由两种生物相容性共聚物Soluplus和普朗尼克F127组成的新型混合胶束系统,以提高难溶性药物芹菜素(AP)作为模型药物的溶解度和口服生物利用度。通过乙醇薄膜水化法制备了载AP混合胶束(AP-M)。在4:1(Soluplus:普朗尼克F127)的比例下,形成的AP-M最佳制剂具有小尺寸(178.5 nm)和球形,并且在水中的溶解度增加到5.61 mg/mL,与游离AP相比增加了约3442倍。AP-M的包封率和载药量分别为95.72%和5.32%,体外释放研究表明AP-M具有缓释特性。跨细胞转运研究表明,在Caco-2细胞转运模型中,AP的细胞摄取增加。AP-M在SD大鼠中的口服生物利用度是游离AP的4.03倍,表明Soluplus和普朗尼克F127的混合胶束是一种在工业上可行的药物递送系统,可促进难溶性药物在胃肠道的口服吸收。

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