İzgü Fatih, Bayram Günce, Tosun Kübra, İzgü Demet
Department of Molecular Biology and Genetics, Middle East Technical University, Ankara, Turkey.
Department of Biotechnology, Graduate School of Natural and Applied Sciences, Middle East Technical University, Ankara, Turkey.
Int J Nanomedicine. 2017 Aug 3;12:5601-5611. doi: 10.2147/IJN.S141949. eCollection 2017.
In this study, a liposomal lyophilized powder formulation of panomycocin was developed for therapeutic purposes against vulvovaginal candidiasis which affects 80% of women worldwide. Panomycocin is a potent antimycotic protein secreted by the yeast NCYC 434. This study involved the preparation of panomycocin-loaded stratum corneum lipid liposomes (SCLLs), characterization of the SCLLs, and determination of antimycotic efficacy of the formulation against and clinical vaginal isolates in a human vaginal epithelium tissue model. The encapsulation and loading efficiencies of SCLLs were 73% and 76.8%, respectively. In transmission electron microscopy images, the SCLLs appeared in the submicron size range. Dynamic light scattering analyses showed that the SCLLs had uniform size distribution. Zeta potential measurements revealed stable and positively charged SCLLs. In Fourier transform infrared spectroscopy analyses, no irreversible interactions between the encapsulated panomycocin and the SCLLs were detected. The SCLLs retained >98% of encapsulated panomycocin in aqueous solution up to 12 hours. The formulation was fungicidal at the same minimum fungicidal concentration values for non-formulated pure panomycocin when tested on an in vitro model of vaginal candidiasis. This is the first study in which SCLLs and a protein as an active ingredient have been utilized together in a formulation. The results obtained in this study led us to conduct further preclinical trials of this formulation for the development of an effective topical anti-candidal drug with improved safety.
在本研究中,开发了一种泛霉素脂质体冻干粉末制剂,用于治疗影响全球80%女性的外阴阴道念珠菌病。泛霉素是酵母NCYC 434分泌的一种强效抗真菌蛋白。本研究涉及制备负载泛霉素的角质层脂质体(SCLLs),对SCLLs进行表征,并在人阴道上皮组织模型中测定该制剂对白色念珠菌和临床阴道分离株的抗真菌效果。SCLLs的包封率和载药率分别为73%和76.8%。在透射电子显微镜图像中,SCLLs呈亚微米尺寸范围。动态光散射分析表明,SCLLs具有均匀的尺寸分布。ζ电位测量显示SCLLs稳定且带正电荷。在傅里叶变换红外光谱分析中,未检测到包封的泛霉素与SCLLs之间存在不可逆相互作用。SCLLs在水溶液中长达12小时保留了>98%的包封泛霉素。当在阴道念珠菌病体外模型上进行测试时,该制剂在与未配制的纯泛霉素相同的最低杀菌浓度值下具有杀菌作用。这是首次在制剂中同时使用SCLLs和蛋白质作为活性成分的研究。本研究获得的结果促使我们对该制剂进行进一步的临床前试验,以开发一种安全性更高的有效局部抗念珠菌药物。