Zhang Xiao, Wu Chen-Chen, Jiang Hua, Zhao Jia-Fu, Pan Zhong-Jian, Zheng Yin
College of Animal Science, Guizhou University, Guiyang, Guizhou, People's Republic of China.
College of Veterinary Medicine, Gansu Agriculture University, Lanzhou, Gansu, People's Republic of China.
Int J Nanomedicine. 2025 Jan 20;20:807-826. doi: 10.2147/IJN.S479514. eCollection 2025.
Adjusting thickening agent proportions in nanoemulsion gel (NG) balances its transdermal and topical delivery properties, making it more effective for dermatophytosis treatment.
Carbomer 940 and α-pinene were used as model thickening agent and antifungal, respectively. A series of α-pinene NGs (αNG1, αNG2, αNG3) containing 0.5%, 0.75% and 1% (w/w) Carbomer 940 were developed and evaluated for stability, rheological properties, and skin irritation; assessed for ex vivo skin permeation, deposition, and fluorescent imaging of drug distribution within skin layers; and tested in vivo for efficacy against infection in guinea pigs, with PAS (Periodic Acid-Schiff) staining confirming fungal clearance.
The steady-state skin flux rates of α-pinene over 24 hours were αNG1 (46.93±2.52 μg/cm²/h) > αNG2 (26.01±2.65 μg/cm²/h) > αNG3 (11.36±1.69 μg/cm²/h). The α-pinene deposition in the epidermis/dermis for αNG1 decreased substantially from 2 h (62.74 ± 3.36 μg/cm²) to 12 h (11.7 ± 2.24 μg/cm²). In contrast, αNG2 showed relatively sustained deposition with 2 h (25.54 ± 2.67 μg/cm²), 6 h (57.32 ± 4.62 μg/cm²) and 12 h (23.69 ± 3.29 μg/cm²). αNG3 exhibited a slow increase from 2 h (18.32 ± 2.11 μg/cm²) to 12 h (36.78 ± 3.22 μg/cm²). The αNG2 exhibited the highest efficacy and fungal clearance rates (71.42%, 79.17%), followed by αNG1 (55.34% and 60.42%), and αNG3(43.21%, 52.08%). Fluorescent imaging confirmed αNG2's higher drug deposition within the epidermis/dermis, while PAS staining showed a potent fungal clearance with αNG2.
This study demonstrates that Carbomer 940 proportions significantly impact the transdermal performance of αNG. αNG2, with a moderate proportion, optimally enhances skin drug delivery and deposition, achieving superior therapeutic outcomes. These findings highlight the importance of optimizing thickening agent proportions to improve the efficacy of topical nanoemulsion gels.
调整纳米乳凝胶（NG）中增稠剂的比例可平衡其透皮和局部给药特性，使其对皮肤癣菌病的治疗更有效。
分别使用卡波姆940和α-蒎烯作为模型增稠剂和抗真菌剂。制备了一系列含有0.5%、0.75%和1%（w/w）卡波姆940的α-蒎烯纳米乳凝胶（αNG1、αNG2、αNG3），并对其稳定性、流变学性质和皮肤刺激性进行了评估；对其进行了离体皮肤渗透、沉积以及药物在皮肤各层内分布的荧光成像评估；并在体内测试了其对豚鼠感染的疗效，用高碘酸希夫（PAS）染色确认真菌清除情况。
α-蒎烯在24小时内的稳态皮肤通量率为αNG1（46.93±2.52μg/cm²/h）>αNG2（26.01±2.65μg/cm²/h）>αNG3（11.36±1.69μg/cm²/h）。αNG1中α-蒎烯在表皮/真皮中的沉积量从2小时（62.74±3.36μg/cm²）大幅下降至12小时（11.7±2.24μg/cm²）。相比之下，αNG2显示出相对持续的沉积，2小时（25.54±2.67μg/cm²）、6小时（57.32±4.62μg/cm²）和12小时（23.69±3.29μg/cm²）。αNG3从2小时（18.32±2.11μg/cm²）到12小时（36.78±3.22μg/cm²）呈缓慢增加。αNG2表现出最高的疗效和真菌清除率（71.42%，79.17%），其次是αNG1（55.34%和60.42%），以及αNG3（43.21%，52.08%）。荧光成像证实αNG2在表皮/真皮内有更高的药物沉积，而PAS染色显示αNG2具有强大的真菌清除能力。
本研究表明卡波姆940的比例显著影响αNG的透皮性能。比例适中的αNG2能最佳地增强皮肤药物递送和沉积，实现卓越的治疗效果。这些发现凸显了优化增稠剂比例以提高局部纳米乳凝胶疗效的重要性。
