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高良姜油 SNEDDS 的制剂优化、麻醉活性、经皮渗透及在斑马鱼 (Danio rerio) 中的转运途径。

Formulation optimization, anesthetic activity, skin permeation, and transportation pathway of Alpinia galanga oil SNEDDS in zebrafish (Danio rerio).

机构信息

Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.

Laboratory of Aquatic Pathobiology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Frederiskberg C, Denmark.

出版信息

Eur J Pharm Biopharm. 2021 Aug;165:193-202. doi: 10.1016/j.ejpb.2021.04.022. Epub 2021 May 9.

Abstract

Alpinia galanga oil (AGO) has an anesthetic activity but its water insoluble property limits its clinical applications. The aim of the present study was to develop a self-nanoemulsifying drug delivery system of AGO (SNEDDS-AGO) to avoid the use of organic solvent and investigate AGO transportation pathway and anesthetic activity. Three optimized formulations from a contour plots of droplet size; SNEDDS-AGO-1, SNEDDS-AGO-2, and SNEDDS-AGO-3, composed of AGO, Miglyol 812, Cremophor RH 40, Capmul MCM EP, and ethanol at the ratios of 40:10:35:10:5, 40:20:15:20:5, and 60:10:15:10:5, respectively were selected as they possessed different droplet size of 62 ± 0.5, 107 ± 2.8, and 207 ± 4.3 nm, respectively. It was found that the droplet size played an important role in fish anesthesia. SNEDDS-AGO-3 showed the longest anesthetic induction time (270 sec) (p < 0.03). Transportation pathway and skin permeation of SNEDDS-AGO-2 were investigated using nile red labelled AGO and detected by fluorescence microscope. AGO was found mostly in brain, gills, and skin suggesting that the transportation pathway of AGO in zebrafish is passing through the gills and skin to the brain. SNEDDS-AGO formulations showed significantly higher permeation through the skin than AGO ethanolic solution. In conclusion, SNEDDS is a promising delivery system of AGO.

摘要

高良姜油(AGO)具有麻醉活性,但由于其不溶于水,限制了其临床应用。本研究旨在开发一种高良姜油自微乳给药系统(SNEDDS-AGO),以避免使用有机溶剂,并研究高良姜油的转运途径和麻醉活性。从粒径等高线图中选择了三个优化的配方,即 SNEDDS-AGO-1、SNEDDS-AGO-2 和 SNEDDS-AGO-3,它们分别由 AGO、Migliol 812、Cremophor RH 40、Capmul MCM EP 和乙醇以 40:10:35:10:5、40:20:15:20:5 和 60:10:15:10:5 的比例组成,它们具有不同的粒径,分别为 62 ± 0.5nm、107 ± 2.8nm 和 207 ± 4.3nm。结果发现,粒径在鱼类麻醉中起着重要作用。SNEDDS-AGO-3 表现出最长的麻醉诱导时间(270 秒)(p < 0.03)。通过尼罗红标记的 AGO 研究了 SNEDDS-AGO-2 的转运途径和皮肤渗透,并通过荧光显微镜进行了检测。发现 AGO 主要存在于大脑、鳃和皮肤中,表明 AGO 在斑马鱼中的转运途径是通过鳃和皮肤进入大脑。SNEDDS-AGO 制剂的皮肤渗透性明显高于 AGO 乙醇溶液。综上所述,SNEDDS 是一种有前途的 AGO 传递系统。

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