Onychomycosis is a progressive fungal infection of the nails that involves the deeper nail layer and nail bed. It is important to maintain sufficient drug concentration in the diseased tissues after topical application. In this study, a stable topical delivery system for efinaconazole (EFN) was designed to enhance absorption potential through the skin and nail plate by incorporating ethanol, diethylene glycol monoethyl ether (Transcutol P) and isopropyl myristate, and cyclomethicone into the topical solution as a delivery vehicle, permeation enhancers, and a wetting agent, respectively. In addition, the stability of EFN in the formulation was significantly improved by adding butylated hydroxytoluene, diethylenetriamine pentaacetic acid, and citric acid as an antioxidant, chelating agent, and pH-adjusting agent, respectively, without discoloration. The optimum EFN formulation (EFN-K) showed 1.46-fold greater human skin permeation than that of the reference control (commercial 10% EFN topical solution). Furthermore, after a 24-hour incubation, the amount of infiltrated EFN from EFN-K in the human nail plate was 4.11-fold greater than that of the reference control, resulting in an 89.7% increase in nail flux at 7 days after treatment. EFN-K significantly accelerated structural recovery of the keratin layer in a Trichophyton mentagrophytes-infected guinea pig onychomycosis model, decreasing the mean viable fungal cell count by 54.3% compared to the vehicle-treated group after once-daily treatment for 4 weeks. Thus, the accelerated skin and nail penetration effect of EFN-K is expected to achieve good patient compliance, and improve the complete cure rate of onychomycosis.

中文翻译：

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高度皮肤和指甲渗透性的依那康唑局部用制剂的制备和体内评价，用于增强甲癣的治疗。

甲癣是指指甲的进行性真菌感染，涉及较深的指甲层和指甲床。局部应用后，在患病组织中保持足够的药物浓度非常重要。在这项研究中，通过将乙醇，二甘醇单乙醚（Transcutol P）和肉豆蔻酸异丙酯和环甲硅油作为外用剂掺入乙醇中，设计了一种稳定的非那康唑（EFN）局部给药系统，以增强通过皮肤和指甲板的吸收潜力。载体，渗透促进剂和润湿剂。另外，通过分别添加丁基化羟基甲苯，二亚乙基三胺五乙酸和柠檬酸作为抗氧化剂，螯合剂和pH调节剂，EFN在制剂中的稳定性得到显着改善，而不会变色。最佳EFN配方（EFN-K）的人体皮肤渗透性比参考对照（商业10％EFN局部溶液）的人皮肤渗透性高1.46倍。此外，在24小时的温育之后，人指甲板中从EFN-K渗透的EFN的量是参考对照的4.11倍，导致在处理后7天指甲通量增加89.7％。EFN-K显着加速了经毛癣菌感染的豚鼠甲癣模型中角蛋白层的结构恢复，相比于媒介物治疗组，每天一次治疗4周后，其平均存活真菌细胞数减少了54.3％。因此，预期EFN-K的皮肤和指甲渗透加速作用可实现良好的患者依从性，并提高灰指甲的完全治愈率。