Amorim Maria Eliza Samuel, Ribeiro Natália de Oliveira Lima, Pinto Flávia Carmo Horta, de Oliveira Pedro Ferreira, Pommini Marcus Vinícius, Siqueira Mateus Boaventura, Bello Zakariyya Muhammad, Fabri Rodrigo Luiz, de Freitas Marcelo Gonzaga, do Couto Renê Oliveira
"Dona Lindu" Midwest Campus, Universidade Federal de São João del-Rei (UFSJ), MG, 35501-296, Divinópolis, Brazil.
Department of Natural Sciences, Dom Bosco Campus, Universidade Federal de São João del-Rei (UFSJ), Divinópolis, MG, Brazil.
Braz J Microbiol. 2025 Aug 18. doi: 10.1007/s42770-025-01764-0.
We evaluated the pre-clinical efficacy of simvastatin (SVT)-loaded emulgels in an in vivo model of azole-resistant Candida albicans (ATCC 10231)-induced vaginal candidiasis and conducted in vitro biopharmaceutical characterization of the most effective formulation. The efficacy of SVT-loaded emulgels (15, 30, and 60 mg/g) was assessed in immunosuppressed Wistar rats with induced candidiasis and compared to commercially available vaginal creams containing clotrimazole (10 mg/g) or nystatin (25,000 IU/g). Products were administered once daily for seven days (n = 5 per group). A high-resolution and sensitive HPLC-PDA method was developed and validated to quantify SVT, determine its solubility in the release medium, and evaluate its in vitro release profile and kinetics. The 60 mg/g SVT-loaded emulgel achieved a 100% reduction in fungal load after 7 days (p < 0.05). SVT solubility in the release medium was 881 ± 36 µg/mL, and its content in the emulgel was 114.95 ± 4.46% m/m. The controlled release kinetics followed Makoid-Banakar's model, indicating an average release rate of 0.036%/h. Therefore, the 60 mg/g SVT-loaded emulgel shows potential as a therapeutic strategy for treating resistant vulvovaginal candidiasis, warranting further clinical studies.
我们在唑类耐药白色念珠菌（ATCC 10231）诱导的阴道念珠菌病体内模型中评估了载有辛伐他汀（SVT）的乳化凝胶的临床前疗效，并对最有效的制剂进行了体外生物药剂学表征。在诱导念珠菌病的免疫抑制Wistar大鼠中评估了载有SVT的乳化凝胶（15、30和60 mg/g）的疗效，并与含有克霉唑（10 mg/g）或制霉菌素（25,000 IU/g）的市售阴道乳膏进行了比较。产品每天给药一次，持续7天（每组n = 5）。开发并验证了一种高分辨率和灵敏的HPLC-PDA方法，用于定量SVT、测定其在释放介质中的溶解度，并评估其体外释放曲线和动力学。7天后，60 mg/g载有SVT的乳化凝胶使真菌载量降低了100%（p < 0.05）。SVT在释放介质中的溶解度为881±36 μg/mL，其在乳化凝胶中的含量为114.95±4.46% m/m。控释动力学遵循Makoid-Banakar模型，表明平均释放速率为0.036%/h。因此，60 mg/g载有SVT的乳化凝胶显示出作为治疗耐药性外阴阴道念珠菌病的治疗策略的潜力，值得进一步进行临床研究。
