Department of Pharmaceutics, National Organization for Drug Control and Research (NODCAR), Cairo, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy October 6th University, Cairo, Egypt.
AAPS PharmSciTech. 2021 Jan 6;22(1):33. doi: 10.1208/s12249-020-01893-9.
Onychomycosis is considered a stubborn nail fungal infection that does not respond to conventional topical antifungal treatments. This study aimed to develop and characterize novel solid lipid nanoparticles (SLNs) formulae containing terbinafine HCl (TFH) and loaded with different nail penetration enhancers (nPEs). Three (nPEs) N-acetyl-L-cysteine, thioglycolic acid, and thiourea were used. Characterization of the prepared formulae was done regarding particle size, zeta potential, polydispersity index (PDI), entrapment efficiency (EE%), physical stability, in vitro release study, infrared (FT-IR), and their morphological structures. The selected formulae and the marketed cream Lamifen® were compared in terms of their antifungal activity against Trichophyton rubrum as well as their nail hydration and their drug uptake by the nail clippers. Thiourea was the nPE of choice; formulae (N2 and N8), with thiourea, were considered the optimum TFH SLNs containing nPEs. They were selected for their optimum particle size of 426.3 ± 10.18 and 450.8 ± 11.45 nm as well as their highest EE% of 89.76 ± 1.25 and 90.35 ± 1.33, respectively. The in vitro microbiological screening of the antifungal activity of these two formulae showed significantly larger zones of inhibition in comparison with the marketed product. The ex vivo screening of the drug uptake of the two selected formulae was significantly higher than that of the marketed product. The nPE formulae present a very promising option as they showed optimum physicochemical characterization with high antifungal activity and high drug uptake as well as good nail hydration effect.
甲真菌病被认为是一种顽固的指甲真菌感染，对常规局部抗真菌治疗无反应。本研究旨在开发和表征含有特比萘芬盐酸盐（TFH）并负载不同指甲渗透增强剂（nPE）的新型固体脂质纳米粒（SLN）配方。使用了三种（nPE）N-乙酰-L-半胱氨酸、巯基乙酸和硫脲。对制备的配方进行了粒径、Zeta 电位、多分散指数（PDI）、包封效率（EE%）、物理稳定性、体外释放研究、红外（FT-IR）和形态结构的表征。在体外对红色毛癣菌的抗真菌活性、指甲水化以及指甲夹的药物摄取方面，对所选配方和市售乳膏 Lamifen®进行了比较。硫脲是首选的 nPE；含有硫脲的配方（N2 和 N8）被认为是含有 nPE 的最佳特比萘芬 SLN。选择它们是因为它们具有最佳的粒径（426.3±10.18nm 和 450.8±11.45nm）和最高的 EE%（89.76±1.25%和 90.35±1.33%）。这两种配方体外微生物学筛选抗真菌活性的结果显示，与市售产品相比，它们的抑菌圈明显更大。两种选定配方的药物摄取的离体筛选结果明显高于市售产品。这些 nPE 配方具有非常有前途的选择，因为它们表现出最佳的物理化学特性，具有高抗真菌活性和高药物摄取率，以及良好的指甲水化效果。
