Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brasil.
Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências da Saúde, Universidade Federal de Santa Maria (UFSM), RS, Brasil.
Eur J Pharm Sci. 2021 Dec 1;167:106011. doi: 10.1016/j.ejps.2021.106011. Epub 2021 Sep 16.
The aim of this study was to evaluate the in vitro antifungal action of a diphenyl diselenide-loaded poly(ε-caprolactone) nanocapsules suspension (NC-1) and incorporate it into a gellan gum hydrogel formulation in order to assess its in vivo efficacy in an animal model of vulvovaginal candidiasis. Nanocapsules suspensions containing the compound (NC-1 ∼ 5 mg/mL) or not (NC-B) were prepared by the interfacial deposition of preformed polymer method. To estimate in vitro antifungal effect, the broth microdilution test was applied. The results showed that NC-1 had equal or lower MIC values when compared to free compound against fifteen Candida strains. Following, the hydrogel was prepared by direct thickening of the nanocapsules suspension by gellan gum addition. The animal model of vulvovaginal candidiasis was induced by infecting female Swiss mice with Candida albicans strains. The animals were topically treated with 20 µL of hydrogels (NC-1 and free compound - 0.1 mg of diphenyl diselenide/once a day for seven days) and then the total fungal burden was assessed after the euthanasia. The results showed that the hydrogels presented pH in the acidic range, compound content close to theoretical value, homogeneous particle distribution with nanometric size, high physicochemical and microbiological stability as well as great bioadhesive property. The nano-based presented superior pharmacological action in comparison to the hydrogel containing non-encapsulated diphenyl diselenide. The results demonstrated that the nanoencapsulation maintained the effective antifungal action of diphenyl diselenide. The nano-based hydrogel formulation may be considered a promising approach against vulvovaginal candidiasis.
本研究旨在评估二苯基二硒纳米胶囊混悬液(NC-1)的体外抗真菌作用,并将其纳入卡拉胶水凝胶制剂中,以评估其在阴道假丝酵母菌病动物模型中的体内疗效。采用界面聚合法制备含药物(NC-1∼5mg/mL)和不含药物(NC-B)的纳米胶囊混悬液。为了评估体外抗真菌效果,采用肉汤微量稀释法进行了研究。结果表明,NC-1 的 MIC 值与游离药物相当或更低,对 15 株念珠菌菌株均有效。随后,通过添加卡拉胶直接增稠纳米胶囊混悬液来制备水凝胶。通过感染雌性瑞士小鼠白色念珠菌菌株来诱导阴道假丝酵母菌病动物模型。动物每天用 20μL 水凝胶(NC-1 和游离药物-0.1mg 二苯基二硒/次,连续 7 天)进行局部治疗,然后在安乐死后评估总真菌负荷。结果表明,水凝胶的 pH 值处于酸性范围,药物含量接近理论值,纳米级的粒径分布均匀,具有较高的物理化学和微生物稳定性以及良好的生物粘附性。与含有未包封二苯基二硒的水凝胶相比,纳米制剂具有更好的药理作用。结果表明,纳米包封维持了二苯基二硒的有效抗真菌作用。纳米水凝胶制剂可能是一种有前途的治疗阴道假丝酵母菌病的方法。