Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. Albert Hall, 159, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. Albert Hall, 159, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
Eur J Pharm Sci. 2020 May 30;148:105323. doi: 10.1016/j.ejps.2020.105323. Epub 2020 Apr 4.
Superficial mycoses are the fungal infections of skin, hair and nail which affect thousands of people worldwide. Emerging resistance to azole antifungals is a common problem in the treatment of superficial or systemic fungal infection. Ebselen (EB), an organoselenium compound, has demonstrated promising activity against pathogenic yeasts. EB showed negligible dynamic and kinetic solubility in water (~ 4.2 µg/mL) which severely limits the scope of conventional formulations. The objective of present study was to develop and characterize a novel topical nanoemulgel of EB for enhancing solubility and permeability. Based on saturation solubility study, EB loaded self-nanoemulsifying preconcentrate (EB-P) was prepared using Dimethylacetamide, Kolliphor® ELP and Medium chain triglyceride which spontaneously formed 54.82 ± 1.26 nm size nanoglobules with zeta potential of -1.69 mV. Nanoemulgel was prepared by homogenous dispersion of EB-P in various gel/ointment bases. Scanning electron microscopy images showed significant drug precipitation in nanoemulgels prepared without Soluplus®. Rheological study confirmed shear thinning behavior of Soluplus® based HPMC K4M (SBH) gel. EB-P loaded SBH showed 2.3 and 5-fold higher Strat-M® deposition of EB compared to HPMC gel and Aquaphor®, respectively. EB-P showed marked anti-fungal activity at 20 µM against Candida albicans and Candida tropicalis while terbinafine was ineffective even at 100 µM concentration. Thus, topical nanoemulgel of EB could be a promising alternative to existing therapy for treatment of candidiasis.
浅部真菌感染是一种影响全球数千人的皮肤、毛发和指甲真菌感染。唑类抗真菌药物的耐药性不断出现，是治疗浅部或系统性真菌感染的常见问题。依布硒啉（EB）是一种有机硒化合物，对致病性酵母菌具有良好的活性。EB 在水中的动力学和溶解度都很低（~4.2μg/mL），这严重限制了传统制剂的应用范围。本研究的目的是开发和表征一种新型的 EB 局部纳米乳凝胶，以提高其溶解度和渗透性。基于饱和溶解度研究，使用二甲基乙酰胺、Kolliphor® ELP 和中链甘油三酯制备了负载 EB 的自微乳前体（EB-P），该前体可自发形成 54.82±1.26nm 大小的纳米球，具有-1.69mV 的 ζ 电位。纳米乳凝胶通过将 EB-P 均匀分散在各种凝胶/软膏基质中制备。扫描电子显微镜图像显示，在没有 Soluplus®的纳米乳凝胶中会出现明显的药物沉淀。流变学研究证实了基于 Soluplus®的 HPMC K4M（SBH）凝胶的剪切稀化行为。与 HPMC 凝胶和 Aquaphor®相比，负载 EB-P 的 SBH 显示出 2.3 和 5 倍更高的 Strat-M® EB 沉积。EB-P 在 20μM 时对白色念珠菌和热带念珠菌表现出显著的抗真菌活性，而特比萘芬即使在 100μM 浓度下也无效。因此，EB 的局部纳米乳凝胶可能是治疗念珠菌病的现有治疗方法的一种有前途的替代方法。
