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杨梅素自微乳给药系统的制剂开发、特性研究、体外和体内评价。

Self-nanoemulsifying drug delivery systems of myricetin: Formulation development, characterization, and in vitro and in vivo evaluation.

机构信息

Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

出版信息

Colloids Surf B Biointerfaces. 2017 Dec 1;160:101-109. doi: 10.1016/j.colsurfb.2017.09.020. Epub 2017 Sep 7.

Abstract

Despite various pharmacological effects, myricetin (Myr) shows low oral bioavailability (<10%) due to its poor solubility, which limits its applications. To address this problem, self-nanoemulsifying drug delivery systems (SNEDDS) were developed by investigating the solubility of Myr in various excipients, constructing pseudo-ternary phase diagrams, and optimizing based on droplet size and emulsification efficacy after drug loading. The obtained Myr-SNEDDS were F04 (Capryol 90/Cremophor RH 40/PEG 400 4:3:3), F08 (Capryol 90/CremophorRH40/1,2-propanediol 4:3:3), F13 (Capryol 90/Cremophor EL/Transcutol HP 4:3:3) and F15 (Capryol 90/Cremephor RH 40/Transcutol HP 2:7:1), with droplet sizes less than 200nm. Additional evaluations showed that these Myr-SNEDDS formulations had fast release properties (over 90% in 1min), low cytotoxicity, and improved permeability and solubility compared with the free drug. Consequently, the oral bioavailabilities of Myr were 5.13, 6.33, 4.69 and 2.53-fold for F04, F08, F13 and F15, respectively, relative to Myr alone. The present study demonstrated that SNEDDS is a viable platform for the oral delivery of insoluble drugs such as Myr.

摘要

尽管杨梅素(Myr)具有多种药理学作用,但由于其溶解度低(<10%),口服生物利用度较低,限制了其应用。为了解决这个问题,通过考察 Myr 在各种赋形剂中的溶解度、构建伪三元相图,并根据载药后粒径和乳化效果进行优化,开发了自微乳给药系统(SNEDDS)。所得的 Myr-SNEDDS 为 F04(Capryol 90/Cremophor RH 40/PEG 400 4:3:3)、F08(Capryol 90/Cremophor RH 40/1,2-丙二醇 4:3:3)、F13(Capryol 90/Cremophor EL/Transcutol HP 4:3:3)和 F15(Capryol 90/Cremophor RH 40/Transcutol HP 2:7:1),粒径均小于 200nm。进一步评价表明,与游离药物相比,这些 Myr-SNEDDS 制剂具有快速释放特性(1min 内超过 90%)、低细胞毒性、以及改善的渗透性和溶解度。因此,与游离药物相比,Myr 的口服生物利用度分别提高了 5.13、6.33、4.69 和 2.53 倍。本研究表明,SNEDDS 是一种可行的平台,可用于递送诸如 Myr 等难溶性药物的口服给药。

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