Köllner S, Nardin I, Markt R, Griesser J, Prüfert F, Bernkop-Schnürch A
ThioMatrix GmbH, Research Center Innsbruck, Trientlgasse 65, 6020 Innsbruck, Austria.
University of Innsbruck, Institute of Pharmacy/Pharmaceutical Technology, CCB - Centrum of Chemistry and Biomedicine, Innrain 80-82, 6020 Innsbruck, Austria.
Eur J Pharm Biopharm. 2017 Jun;115:268-275. doi: 10.1016/j.ejpb.2017.03.012. Epub 2017 Mar 18.
The aim of this study was to develop a vaginal self-emulsifying delivery system for curcumin being capable of spreading, of permeating the mucus gel layer and of protecting the drug being incorporated in oily nanodroplets towards mucus interactions and immobilization.
The emulsifying properties of curcumin loaded SEDDS containing 30% Cremophor RH40, 20% Capmul PG-8, 30% Captex 300, 10% DMSO and 10% tetraglycol (SEDD formulation A) as well as 25% PEG 200, 35% Cremophor RH40, 20% Captex 355, 10% Caprylic acid and 10% Tween 80 (SEDD formulation B) after diluting 1+2 with artificial vaginal fluid were characterized regarding droplet size and zeta potential. Collagen swelling test was used to examine the irritation potential of SEDDS. Additionally to mucus binding studies, permeation studies in the mucus were performed. Furthermore, spreading potential of the novel developed formulations was compared with a commercial available o/w cream (non-ionic hydrophilic cream) on vaginal mucosa.
SEDDS displayed a mean droplet size between 38 and 141nm and a zeta potential of -0.3 to -1.6mV. The collagen swelling test indicated no significant irritation potential of both formulations over 24h. An immediate interaction of unformulated curcumin with the mucus was determined, whereas both SEDDS facilitated drug permeation through the mucus layer. Formulation B showed a 2.2-fold improved transport ratio of curcumin compared to SEDD formulation A. In comparison to the vaginal cream, SEDD formulation A and B were able to spread over the vaginal mucosa and cover the tissue to a 17.8- and 14.8-fold higher extent, respectively.
According to these results, SEDDS seems to be a promising tool for vaginal application.
本研究的目的是开发一种姜黄素阴道自乳化给药系统，该系统能够扩散、渗透黏液凝胶层，并保护油性纳米液滴中所含药物免受黏液相互作用和固定作用的影响。
将含有30%聚氧乙烯氢化蓖麻油RH40、20%辛酸癸酸甘油三酯、30%辛酸癸酸三甘油酯、10%二甲基亚砜和10%四甘醇的载姜黄素自乳化药物递送系统（SEDD制剂A）以及含有25%聚乙二醇200、35%聚氧乙烯氢化蓖麻油RH40、20%辛酸癸酸三甘油酯、10%辛酸和10%吐温80的制剂（SEDD制剂B）用人工阴道液按1+2稀释后，对其液滴大小和zeta电位进行表征。采用胶原蛋白肿胀试验检测SEDD的刺激潜力。除了进行黏液结合研究外，还进行了在黏液中的渗透研究。此外，将新开发制剂的扩散潜力与市售的水包油乳膏（非离子亲水性乳膏）在阴道黏膜上进行比较。
SEDD的平均液滴大小在38至141nm之间，zeta电位为-0.3至-1.6mV。胶原蛋白肿胀试验表明，两种制剂在24小时内均无明显刺激潜力。未配制的姜黄素与黏液立即发生相互作用，而两种SEDD均促进药物透过黏液层。与SEDD制剂A相比,制剂B的姜黄素转运率提高了2.2倍。与阴道乳膏相比，SEDD制剂A和B能够分别在阴道黏膜上扩散，覆盖组织的范围分别高出17.8倍和14.8倍。
根据这些结果，SEDD似乎是一种有前景的阴道给药工具。
