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Enhanced Targeting, Retention, and Penetration of Amphotericin B Through a Biomimetic Strategy to Treat Against Vulvovaginal Candidiasis
Advanced Therapeutics ( IF 4.6 ) Pub Date : 2022-09-19 , DOI: 10.1002/adtp.202200086
Yijing Lin 1 , Qingqing Yin 1 , Deli Zhuge 2 , Yiqin Hu 1 , Xuewei Yang 1 , Dongyan Tian 1 , Li Li 1 , Haonan Wang 2 , Shuangshuang Liu 1 , Cuiye Weng 3 , Xufei Zhang 3 , Bin Wen 3 , Fang Wang 1 , Linzhi Yan 1 , Mengchun Chen 1, 2, 4 , Ledan Wang 1 , Yijie Chen 1, 2
Affiliation  

An effective therapeutic strategy to treat vulvovaginal candidiasis (VVC) that is mainly caused by Candida albicans (C. albicans) infection is highly desirable. While Amphotericin B (AmB) has demonstrated promise, its precise localization to C. albicans burden at vaginal sites is oftentimes limited by the high fluidity microenvironment of the vagina, which can compromise treatment efficacy. To overcome this issue, a biomimetic AmB delivery system is developed, in which AmB preloaded polymeric cores are cloaked with vaginal epithelial cells membrane (VM-ANP). With its cell membrane coating, VM-ANP naturally targets and strongly binds with C. albicans, thus resisting the self-cleaning of vaginal fluid. Besides its long retention property, VM-ANP could penetrate deeply in vaginal tissue to achieve its full antifungal potential by attaching to hidden C. albicans. It is shown that both C. albicans suspension and biofilm biomass could be effectively inhibited by the VM-ANP in vitro. In a C. albicans intravaginal infection model, treatment with VM-ANP results in significantly decreased fungal challenges both in vaginal tissue and fluid. Overall, such biomimetic strategy adds the merit of natural cell membrane into the targeted delivery of drug in treating VVC, which also serves as a promising platform against vaginitis-related pathogens.

中文翻译:

通过仿生策略增强两性霉素 B 的靶向、保留和渗透以治疗外阴阴道念珠菌病

非常需要一种有效的治疗策略来治疗主要由白色念珠菌( C. albicans ) 感染引起的外阴阴道念珠菌病 (VVC)。虽然两性霉素 B (AmB) 已显示出前景,但其对阴道部位白色念珠菌负荷的精确定位通常受到阴道高流动性微环境的限制,这可能会影响治疗效果。为了克服这个问题,开发了一种仿生 AmB 递送系统,其中 AmB 预装聚合物核心被阴道上皮细胞膜 (VM-ANP) 覆盖。凭借其细胞膜涂层,VM-ANP 自然靶向并与白色念珠菌紧密结合,从而抵抗阴道液的自我清洁。除了其长期保留特性外,VM-ANP 还可以深入渗透到阴道组织中,通过附着在隐藏的白色念珠菌上来发挥其全部抗真菌潜力。结果表明,VM-ANP 在体外可有效抑制白色念珠菌悬浮液和生物膜生物质。白色念珠菌阴道内感染模型中,用 VM-ANP 治疗可显着减少阴道组织和液体中的真菌挑战。总的来说,这种仿生策略将天然细胞膜的优点添加到治疗 VVC 的药物靶向递送中,这也可作为对抗阴道炎相关病原体的有前途的平台。
更新日期:2022-09-19
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