1. Development of ROS-sensitive capofungin hydrogel by crosslinking chitosan with four-arm polyethylene glycol derivative for treatment of vulvovaginal candidiasis.
- Author
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Pan H, Xu J, Wang R, Cheng M, Wang Y, and Song B
- Subjects
- Female, Animals, Mice, Caspofungin pharmacology, Caspofungin chemistry, Cross-Linking Reagents chemistry, Rheology, Microbial Sensitivity Tests, Biofilms drug effects, Chitosan chemistry, Chitosan pharmacology, Reactive Oxygen Species metabolism, Polyethylene Glycols chemistry, Candidiasis, Vulvovaginal drug therapy, Candidiasis, Vulvovaginal microbiology, Candida albicans drug effects, Antifungal Agents pharmacology, Antifungal Agents chemistry, Hydrogels chemistry
- Abstract
Both exogenous and endogenous reactive oxygen species (ROS) in vulvovaginal candidiasis (VVC) play pivotal roles in promoting the hyphal formation of Candida albicans (CA), which suggests that clearing ROS could inhibit CA hyphae formation. A ROS-sensitive hydrogel (CAS@4Arm-PB/CS) was formulated by using a novel four-arm polyethylene glycol (4Arm-PEG) derivative (4Arm-PB) as a crosslinking agent, chitosan (CS) as the hydrogel matrix, and caspofungin (CAS) as the antifungal drug against CA. The ROS-sensitivity, disintegration mechanism, crosslinking action, swelling degree, microstructure, modulus, and rheological properties of 4Arm-PB were characterized. According to the results, 5.0 % 4Arm-PB could quickly and efficiently cross-link 0.5 mg/mL of CS. The ROS-sensitivity of 4Arm-PB was 10-50 μM, indicating a strong ROS sensitivity. The in vitro and in vivo anti-CA results indicated that CAS@4Arm-PB/CS not only cleared endogenous and exogenous ROS and inhibited the formation of CA hyphae and biofilm but also contributed beneficially to the treatment of VVC mice caused by CA infection, implying a certain safety aspect and an in vivo applicability. This research introduces a novel functional crosslinking agent for CS hydrogel formulation, presenting a new avenue for hydrogel-based drug delivery systems and therapeutic strategies for VVC treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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