Co-delivery of evodiamine and rutaecarpine in a microemulsion-based hyaluronic acid hydrogel for enhanced analgesic effects on mouse pain models

被引:29
|
作者
Zhang, Yong-Tai [1 ]
Li, Zhe [1 ]
Zhang, Kai [1 ]
Zhang, Hong-Yu [1 ]
He, Ze-Hui [1 ]
Xia, Qing [1 ]
Zhao, Ji-Hui [1 ]
Feng, Nian-Ping [1 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Dept Pharmaceut Sci, Shanghai 201203, Peoples R China
基金
中国国家自然科学基金;
关键词
Nanocarrier; Transdermal delivery; Evodiamine; Rutaecarpine; Prostaglandin; Interleukin; Tumor necrosis factor; IN-VIVO EVALUATION; TRANSDERMAL DRUG-DELIVERY; NONIONIC MICROEMULSIONS; TOPICAL DELIVERY; DERMAL DELIVERY; SKIN DELIVERY; VITRO; FORMULATION; EXTRACT; SYSTEMS;
D O I
10.1016/j.ijpharm.2017.05.064
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of this study was to improve the analgesic effect of evodiamine and rutaecarpine, using a microemulsion-based hydrogel (ME-Gel) as the transdermal co-delivery vehicle, and to assess hyaluronic acid as a hydrogel matrix for microemulsion entrapment. A microemulsion was formulated with ethyl oleate as the oil core to improve the solubility of the alkaloids and was loaded into a hyaluronic acid-structured hydrogel. Permeation-enhancing effects of the microemulsion enabled evodiamine and rutaecarpine in ME-Gel to achieve 2.60-and 2.59-fold higher transdermal fluxes compared with hydrogel control (p < 0.01). The hyaluronic acid hydrogel-containing microemulsion exhibited good skin biocompatibility, whereas effective ME-Gel co-delivery of evodiamine and rutaecarpine through the skin enhanced the analgesic effect in mouse pain models compared with hydrogel. Notably, evodiamine and rutaecarpine administered using ME-Gel effectively down-regulated serum levels of prostaglandin E2, interleukin 6, and tumor necrosis factor a in formaldehyde-induced mouse pain models, possibly reflecting the improved transdermal permeability of ME-Gel co-delivered evodiamine and rutaecarpine, particularly with hyaluronic acid as the hydrogel matrix. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:100 / 106
页数:7
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