São Paulo State University (UNESP), School of Pharmaceutical Sciences, 14800-903, Araraquara, São Paulo, Brazil.
Department of Biosciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, 13414-903, Brazil.
Med Mycol. 2021 Jul 14;59(8):821-827. doi: 10.1093/mmy/myab006.
The present study reports the performance of the pigment hypericin (HYP)-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system (LCPS) for the treatment of vulvovaginal candidiasis (VVC) in mice. LCPS composed of 40% of ethoxylated and propoxylated cetyl alcohol, 30% of oleic acid and cholesterol (7:1), 30% of a dispersion of 16% poloxamer 407 and 0.05% of HYP (HYP-LCPS) was prepared and characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and ex vivo permeation and retention studies across vaginal porcine mucosa were performed. In addition, the antifungal properties of the HYP-LCPS were evaluated in a murine in vivo model; for this, infected C57BL female mice groups were treated with both HYP in solution and HYP-LCPS, and after 6 days colony forming unit (CFU)/ml count was performed. PLM and SAXS confirmed that HYP-LCPS is a microemulsion situated in boundary transition region confirming its action as an LCPS. When in contact with simulated vaginal fluid, HYP-LCPS became rigid and exhibited maltase crosses and bragg peaks characteristics of lamellar phase. Ex vivo permeation and retention studies showed that HYP-LCPS provides a localized treatment on the superficial layers of porcine vaginal mucosa. HYP-LCPS induced a significant reduction in the number of CFU/ml in the mice; thus this formulation indicated it is as effective as a commercial dosage form. It was concluded that LCPS maintains the biological activity of HYP and provides an adequate drug delivery system for this lipophilic molecule at the vaginal mucosa, being a promising option in cases of VVC.
本研究报道了负载金丝桃素（HYP）的泊洛沙姆基黏膜粘附原位凝胶液晶前体系统（LCPS）治疗小鼠阴道念珠菌病（VVC）的性能。LCPS 由 40%乙氧基化和丙氧基化鲸蜡醇、30%油酸和胆固醇（7:1）、30%16%泊洛沙姆 407 分散体和 0.05%HYP（HYP-LCPS）组成，并通过偏光显微镜（PLM）、小角 X 射线散射（SAXS）和阴道猪黏膜的体外渗透和保留研究进行了表征。此外，还在小鼠体内模型中评估了 HYP-LCPS 的抗真菌特性；为此，用溶液中的 HYP 和 HYP-LCPS 治疗感染 C57BL 雌性小鼠组，然后进行菌落形成单位（CFU）/ml 计数。PLM 和 SAXS 证实 HYP-LCPS 是位于边界过渡区的微乳液，证实其作为 LCPS 的作用。当与模拟阴道液接触时，HYP-LCPS 变得坚硬，并表现出麦芽糖交叉和布拉格峰特征的层状相。体外渗透和保留研究表明，HYP-LCPS 对猪阴道黏膜的浅表层提供局部治疗。HYP-LCPS 可显著降低小鼠 CFU/ml 的数量；因此，该制剂表明其与商业剂型一样有效。研究结果表明，LCPS 保持了 HYP 的生物活性，并为亲脂性分子在阴道黏膜提供了足够的药物传递系统，是治疗 VVC 的一种有前途的选择。
