Departamento de Farmacia y Tecnología Farmacéutica, University of Santiago de Compostela, Santiago de Compostela, Spain.
Eur J Pharm Biopharm. 2013 Apr;83(3):370-7. doi: 10.1016/j.ejpb.2012.11.004. Epub 2012 Nov 29.
This work investigated the use of in situ gelling hydrogels based on polypseudorotaxanes of Pluronic F-127 and partially methylated β-cyclodextrin as aqueous nail lacquers. N-acetylcysteine and urea were incorporated as penetration enhancers. The formulations were tested for their ability to deliver ciclopirox and triamcinolone across human nail plate and bovine hoof. Simple aqueous solutions of the drugs with N-acetylcysteine provided measurable fluxes across hoof membranes but became quickly depleted of drug. Further, these solutions would have a short residence time upon nail application. Addition of Pluronic F-127 facilitated drug solubilization and provided the formulations with in situ gelling properties but drug entrapment into the micelles slowed down the delivery process. This was solved by addition of methylated β-cyclodextrin; the formulations retained the thermogelling properties, drug solubilization was further increased, and drug delivery was accelerated. The polymer chains compete with the drugs for the cyclodextrin cavity forming polypseudorotaxanes, which facilitated drug release. The permeability of both drugs was higher across bovine hoof than human nail. The new polypseudorotaxanes formulation delivered more ciclopirox across human nail than a marketed organic lacquer which supports the growing hypothesis that aqueous-based nail lacquers represent a superior formulation strategy in nail topical delivery.
本研究考察了基于泊洛沙姆 F-127 和部分甲基化β-环糊精的假轮烷原位凝胶作为水性指甲漆的用途。将乙酰半胱氨酸和尿素掺入作为渗透增强剂。测试了这些制剂将环吡罗司和曲安奈德递送至人指甲板和牛蹄的能力。含药和乙酰半胱氨酸的简单水性溶液提供了可测量的跨蹄膜通量，但药物很快耗尽。此外，这些溶液在指甲应用时的停留时间很短。添加泊洛沙姆 F-127 有助于药物溶解，并为制剂提供原位凝胶特性，但药物被胶束包埋会减缓药物传递过程。通过添加甲基化β-环糊精解决了这个问题；制剂保留了热凝胶特性，进一步增加了药物溶解，加速了药物传递。聚合物链与药物竞争环糊精腔，形成假轮烷，从而促进药物释放。两种药物在牛蹄上的渗透性均高于人指甲。新型假轮烷制剂在人指甲上递送的环吡罗司比市售有机漆更多，这支持了水基指甲漆在指甲局部递送上代表更优制剂策略的不断增长的假说。
