Department of Biomedical Engineering, College of Engineering, The University of Texas at El Paso, 500 W University Ave, El Paso, TX 79968, USA.
Department of Pharmaceutical Sciences, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA.
Molecules. 2019 Aug 29;24(17):3139. doi: 10.3390/molecules24173139.
Global incidence of superficial fungal infections caused by dermatophytes is high and affects around 40 million people. It is the fourth most common cause of infection. Clotrimazole, a broad spectrum imidazole antifungal agent is widely used to treat fungal infections. Conventional topical formulations of clotrimazole are intended to treat infections by effective penetration of drugs into the stratum corneum. However, drawbacks such as poor dermal bioavailability, poor penetration, and variable drug levels limit the efficiency. The present study aims to load clotrimazole into ufosomes and evaluate its topical bioavailability. Clotrimazole loaded ufosomes were prepared using cholesterol and sodium oleate by thin film hydration technique and evaluated for size, polydispersity index, and entrapment efficiency to obtain optimized formulation. Optimized formulation was characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Skin diffusion studies and tape-stripping were performed using human skin to determine the amount of clotrimazole accumulated in different layers of the skin. Results showed that the optimized formulation had vesicle size <250 nm with ~84% entrapment efficiency. XRD and DSC confirmed the entrapment of clotrimazole into ufosomes. No permeation was observed through the skin up to 24 h following the permeation studies. Tape-stripping revealed that ufosomes led to accumulation of more clotrimazole in the skin compared to marketed formulation (Perrigo). Overall, results revealed the capability of ufosomes in improving the skin bioavailability of clotrimazole.
全球由皮肤真菌引起的浅部真菌感染发病率很高，影响约 4000 万人。它是第四大常见感染原因。克霉唑是一种广谱咪唑类抗真菌药物，广泛用于治疗真菌感染。传统的克霉唑局部制剂旨在通过药物有效渗透到角质层来治疗感染。然而，不足之处如皮肤生物利用度差、渗透差和药物水平变化限制了其效率。本研究旨在将克霉唑载入超滤体并评估其局部生物利用度。采用薄膜水化技术，用胆固醇和油酸钠制备克霉唑超滤体，并对其粒径、多分散指数和包封效率进行评价，以获得优化的配方。采用扫描电子显微镜（SEM）、X 射线衍射（XRD）和差示扫描量热法（DSC）对优化配方进行表征。采用人体皮肤进行皮肤扩散研究和胶带剥离，以确定不同皮肤层中累积的克霉唑量。结果表明，优化配方的囊泡粒径<250nm，包封效率约为 84%。XRD 和 DSC 证实克霉唑被包载入超滤体。在渗透研究中，在 24 小时内没有观察到药物通过皮肤渗透。胶带剥离结果表明，与市售制剂（Perrigo）相比，超滤体使更多的克霉唑在皮肤中积累。总的来说，结果表明超滤体能够提高克霉唑在皮肤中的生物利用度。
