Thapa Raj Kumar, Han Sang-Duk, Park Hyoung Geun, Son Miwon, Jun Joon Ho, Kim Jong Oh
College of Pharmacy, Yeungnam University.
Chem Pharm Bull (Tokyo). 2015;63(7):525-30. doi: 10.1248/cpb.c15-00108. Epub 2015 May 9.
Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.
皮肤真菌感染若不治疗可能会变得严重。有效的皮肤真菌感染治疗方法有助于抗真菌药物深入渗透到有活力的皮肤层。特比萘芬是一种杀菌剂，可抑制麦角甾醇，这是真菌的一种重要成分。本研究的主要目的是评估含有壳聚糖作为成膜剂的特比萘芬溶液的皮肤渗透和滞留情况。使用制备的制剂（DA 5505）和市售的特比萘芬制剂在小鼠和猪皮肤中进行皮肤渗透和滞留的比较评估。为模拟皮肤真菌感染，在NC/Nga小鼠中诱导形成角质化皮肤。与市售制剂相比，DA 5505表现出明显更好的皮肤渗透性。与市售制剂相比，DA 5505显著提高了特比萘芬的通量、渗透系数和增强比，且滞后时间显著缩短。与市售溶液相比，DA 5505显著增加了特比萘芬在有活力皮肤层中的累积滞留量，表明疗效增强。此外，DA 5505在正常皮肤和角质化皮肤中均表现出优异的皮肤渗透性。因此，DA 5505制剂有潜力将特比萘芬有效地递送至浅表和深部皮肤真菌感染部位。
