Ali Mohd Shoab, Rehman Urushi, Gupta Garima, Alsayari Abdulrhman, Wahab Shadma, Goh Khang Wen, Kesharwani Prashant
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.
Graphic Era Hill University, Dehradun, 248002, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug 14. doi: 10.1007/s00210-025-04505-0.
Chronic fungal nail infections like onychomycosis are challenging to treat due to drug resistance, long treatment durations, and poor nail penetration of conventional antifungals. Here, we report the formulation and evaluation of a thymoquinone-loaded ufasome hydrogel (TQ-UFs-Gel) designed for enhanced transungual delivery. TQ-UFs were prepared by thin-film hydration of sodium oleate and cholesterol, optimized via a central composite design to yield vesicles ~ 191.50 ± 0.23 nm in size with 80.05 ± 0.34% entrapment efficiency and PDI 0.18 ± 0.32. The hydrogel was formed by incorporating TQ-UFs into 1% Carbopol 940. Physicochemical characterization included pH, spreadability, viscosity, texture profile analysis, in vitro release (Franz diffusion), ex vivo bovine hoof permeation, nail clipping drug loading, and HET-CAM irritation testing. The optimized TQ-UFs-Gel exhibited shear-thinning behavior (viscosity 987 → 387 cP), pH 5.9 ± 0.23, spreadability 8.7 ± 0.12 cm, and firmness 191.7 g. In vitro release showed a biphasic profile (39.90% in 2 h; 90.10% in 24 h), fitting the Korsmeyer-Peppas model (R = 0.9537). Ex vivo studies demonstrated 95.20 ± 0.8% cumulative permeation and flux 3.29 µg/cm/h, versus 70.30 ± 0.2% and 2.97 µg/cm/h for control gel. Nail clipping analysis confirmed increased TQ loading (1.43 µg/mg vs. 0.68 µg/mg for free TQ). Antifungal assays against Trichophyton mentagrophytes showed a significant CFU reduction for TQ-UFs compared to free drug, and HET-CAM tests indicated minimal irritation (IrS 0.41 ± 1.20). TQ-UFs-Gel demonstrated sustained release, enhanced nail permeation, and antifungal activity with low irritation potential, supporting its potential as a transungual delivery system for onychomycosis treatment.
像甲癣这样的慢性真菌性指甲感染，由于耐药性、治疗时间长以及传统抗真菌药物的指甲穿透性差，治疗起来颇具挑战性。在此，我们报告了一种用于增强经指甲递送的载有百里醌的不饱和脂肪酸囊泡水凝胶（TQ-UFs-Gel）的配方及评估。TQ-UFs通过油酸钠和胆固醇的薄膜水化法制备，经由中心复合设计进行优化，得到大小约为191.50±0.23纳米的囊泡，包封率为80.05±0.34%，多分散指数为0.18±0.32。水凝胶是通过将TQ-UFs掺入1%的卡波姆940中形成的。物理化学特性包括pH值、铺展性、粘度、质地剖面分析、体外释放（弗兰兹扩散）、离体牛蹄渗透、指甲剪片药物负载以及鸡胚绒毛尿囊膜刺激试验。优化后的TQ-UFs-Gel表现出剪切变稀行为（粘度987→387厘泊），pH值为5.9±0.23，铺展性为8.7±0.12厘米，硬度为191.7克。体外释放呈现双相特征（2小时内释放39.90%；24小时内释放90.10%），符合Korsmeyer-Peppas模型（R = 0.9537）。离体研究表明累积渗透率为95.20±0.8%，通量为3.29微克/平方厘米/小时，而对照凝胶分别为70.30±0.2%和2.97微克/平方厘米/小时。指甲剪片分析证实TQ负载量增加（1.43微克/毫克，而游离TQ为0.68微克/毫克）。针对须癣毛癣菌的抗真菌试验表明，与游离药物相比，TQ-UFs的菌落形成单位显著减少，鸡胚绒毛尿囊膜试验表明刺激性极小（刺激指数0.41±1.20）。TQ-UFs-Gel显示出持续释放、增强的指甲渗透性和抗真菌活性，且刺激性低，这支持了其作为治疗甲癣的经指甲递送系统的潜力。
