The University of Mississippi, School of Pharmacy, University, Mississippi, USA.
Institute for Drug Delivery and Biomedical Research, Bangalore, India.
AAPS PharmSciTech. 2017 Oct;18(7):2702-2705. doi: 10.1208/s12249-017-0752-y. Epub 2017 Mar 13.
AR-12 is a novel small molecule with broad spectrum antifungal activity. Recently, AR-12 was found to be highly active against Trichophyton rubrum, one of the predominantly responsible organisms that cause onychomycosis. The primary objective of this project was to investigate the ability of AR-12 to penetrate into and across the human nail plate followed by improving its trans-ungual permeation using different penetration enhancers. TranScreen-N™, a high throughput screening method was utilized to explore the potential nail penetration enhancers to facilitate the drug delivery through the nail. This screen demonstrated that dexpanthenol and PEG 400 were the most efficient enhancers. The in vitro permeation studies were performed across the human cadaver nail plates for 7 days with three AR-12 (5% w/v) formulations containing 10% w/v dexpanthenol (Formulation A), 10% w/v PEG 400 (Formulation B), and a combination of 10% w/v dexpanthenol + 10% w/v PEG 400 (Formulation C). The in vitro studies concluded that dexpanthenol and PEG 400 were able to deliver a significant amount of AR-12 into and across the nail plate that was found to be more than MIC 50 level of the drug.
AR-12 是一种具有广谱抗真菌活性的新型小分子药物。最近，研究发现 AR-12 对引起甲真菌病的主要病原体之一红色毛癣菌具有高度活性。该项目的主要目的是研究 AR-12 穿透并穿过人指甲板的能力，然后使用不同的渗透增强剂来提高其跨甲渗透性。TranScreen-N™是一种高通量筛选方法，用于探索潜在的指甲渗透增强剂，以促进药物通过指甲的输送。该筛选表明，泛醇和聚乙二醇 400 是最有效的增强剂。将三种含有 5% w/v AR-12 的制剂（分别含有 10% w/v 泛醇的制剂 A、10% w/v 聚乙二醇 400 的制剂 B 以及 10% w/v 泛醇+10% w/v 聚乙二醇 400 的制剂 C）进行了为期 7 天的体外渗透研究，研究了它们穿过人尸体指甲板的渗透情况。体外研究表明，泛醇和聚乙二醇 400 能够将大量的 AR-12 递送到指甲板中并穿过指甲板，研究发现药物的浓度超过了 MIC50 水平。
