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活性氧敏感纳米胶束增强酮康唑对阴道假丝酵母菌病中白色念珠菌的抗真菌活性。

Reactive oxygen species sensitive nanomicelles promote the antifungal activity of ketoconazole against Candida albicans in vulvovaginal candidiasis.

机构信息

School of Pharmacy, Weifang Medical University, Baotong Street, No. 7166, Weifang 261053, China.

School of Pharmacy, Weifang Medical University, Baotong Street, No. 7166, Weifang 261053, China.

出版信息

Colloids Surf B Biointerfaces. 2024 Nov;243:114140. doi: 10.1016/j.colsurfb.2024.114140. Epub 2024 Aug 5.

DOI:10.1016/j.colsurfb.2024.114140
PMID:39111157
Abstract

Excessive local accumulation of reactive oxygen species (ROS) in vulvovaginal candidiasis (VVC) leads to oxidative stress and aggravates inflammation. This study aimed to optimize and synthesize four ROS-sensitive polyethylene glycol (PEG)-boride polymers (PB, PCB, BPB, and BCPCB). A nanomicelle (BCPCB-K) was constructed using BCPCB-encapsulated ketoconazole (KTZ). Finally, the depolymerization principle and ROS-sensitive drug release of BCPCB-K as well as its anti-Candida albicans (CA) and therapeutic effects on mice with VVC were explored through in vitro and in vivo experiments. BCPCB-K exhibited low toxicity to mammalian cells in vitro and good biocompatibility in vivo. It also improved the dispersion and solubility of the hydrophobic drug KTZ. Furthermore, BCPCB-K simultaneously scavenged ROS and released the drug, thus facilitating the antifungal and VVC-treating effects of KTZ. Overall, the findings of this study broadened the application of ROS-sensitive materials in the drug-loading and antifungal fields and provided a strategy for VVC treatment.

摘要

外阴阴道假丝酵母菌病(VVC)中活性氧(ROS)的过度局部积累会导致氧化应激,加重炎症。本研究旨在优化和合成四种 ROS 敏感的聚乙二醇(PEG)-硼化物聚合物(PB、PCB、BPB 和 BCPCB)。使用包裹酮康唑(KTZ)的 BCPCB 构建了纳米胶束(BCPCB-K)。最后,通过体外和体内实验探讨了 BCPCB-K 的解聚原理、ROS 敏感药物释放及其对 VVC 小鼠的抗白色念珠菌(CA)和治疗作用。BCPCB-K 在体外对哺乳动物细胞的毒性低,体内生物相容性好。它还改善了疏水性药物 KTZ 的分散性和溶解性。此外,BCPCB-K 同时清除 ROS 并释放药物,从而增强了 KTZ 的抗真菌和 VVC 治疗效果。总的来说,本研究结果拓宽了 ROS 敏感材料在药物负载和抗真菌领域的应用,并为 VVC 治疗提供了一种策略。

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