L-Se-methylselenocysteine loaded mucoadhesive thermogel for effective treatment of Vulvar candidiasis
L-Se-methylselenocysteine loaded mucoadhesive thermogel for effective treatment of Vulvar candidiasis
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L-Se-甲基硒代半胱氨酸负载粘膜粘附热凝胶可有效治疗外阴念珠菌病
DOI：
10.1016/j.ijpharm.2022.121851
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发表时间：
2022-05-26
影响因子：
5.8
通讯作者：
Zhang，Jiye
中科院分区：
文献类型：
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作者：
Yang，Xianwei;Wang，Menghan;Zhang，Jiye
外阴念珠菌病（VVC）是由阴道粘膜念珠菌感染引起的阴道炎，严重危害妇女健康。尽管市场上噻唑类药物越来越多，但仍缺乏新的抗真菌药物，治疗唑类耐药念珠菌阴道炎仍具有挑战性。结果表明，L-Se-甲基硒代半胱氨酸（L-SeMC）能有效抑制白念珠菌的生长，使菌丝密度和长度降低。为了延长L-硒MC在阴道内的滞留时间，提高其对VVC的治疗效果，成功合成并制备了粘膜粘附热凝胶（NAC-HA热凝胶）。负载L-SeMC的粘膜粘附热凝胶（L-SeMC@NAC-HA热凝胶）的凝胶化窗口为约29-56 °C，其在体外释放研究中表现出持续释放曲线，并且在阴道中的保留时间延长。此外，L-SeMC@NAC-HA热凝胶在体内安全性研究中表现出良好的安全性。在大鼠VVC模型中检测L-SeMC@NAC-HA热凝胶的体内抗VVC作用，L-SeMC@NAC-HA热凝胶显著减少阴道分泌物中白色念珠菌的数量，减轻阴道损伤，并减少促炎因子（TNF-α、IL-1α和IL-β）的分泌。因此，在不久的将来，它是一种有希望的治疗VVC的临床治疗方法。
Vulvar candidiasis (VVC) is a vaginitis caused by vaginal mucosa infection of Candida, which greatly impairs women's health. Although there are more and more thiazoles on the market, new classes of antifungal drugs are still missing, it is still challenging to treat azole-resistant candidal vaginitis. We found that L-Se-methylselenocysteine (L-SeMC) could effectively inhibit the growth of Candida albicans, reduce the density and length of the mycelia. To extend the retention time of L-SeMC in the vaginal tract and enhance its therapeutic effect for VVC, a mucoadhesive thermogel (NAC-HA thermogel) was successfully synthesized and prepared. The gelation window was around 29–56 °C for L-SeMC loaded mucoadhesive thermogel (L-SeMC@NAC-HA thermogel), which exhibited a sustained release profile in thein vitrorelease study and an extended retention time in the vaginal tract. Besides, L-SeMC@NAC-HA thermogel exhibited a good safety profile in thein vivosafety study. Thein vivoanti-VVC effect was examined in a rat VVC model and L-SeMC@NAC-HA thermogel significantly reduced the number of Candida albicans in the vaginal secreta, mitigated the vaginal damage and reduced the secretion of proinflammatory factors (TNF-α, IL-1α and IL-β). Therefore, it is a promising therapy for the clinical treatment of VVC in the near future.