Enhancing Therapeutic Efficacy of Cinnamon Essential Oil by Nanoemulsification for Intravaginal Treatment of Candida Vaginitis
Yi‐Ting Lin, Wei‐Chung Tsai, Hsueh-Yu Lu, Shih‐Yuan Fang, Hsiang-Wen Chan, Chung‐Hsiung Huang
Abstract
Background: Due to its prevalence, recurrence, and the emergence of drug-resistance, Candida vaginitis significantly impacts the well-being of women. Although cinnamon essential oil (CEO) possesses antifungal activity, its hydrophobic properties limit its clinical application. Purpose: To overcome this challenge, a nanoemulsification technology was employed to prepare cinnamon essential oil-nanoemulsion (CEO@NE), and its therapeutic efficacy and action mechanism for Candida vaginitis was investigated in vivo and in vitro. Materials and Methods: CEO@NE, composed of 4% CEO, 78% distilled water, and 18% Tween 80, was prepared by ultrasonic nanoemulsification. The physical properties, anti- Candida activity, cytotoxicity, immunomodulatory potential and storage stability of CEO@NE were explored. Subsequently, the effect of intravaginal CEO@NE treatment on Candida vaginitis was investigated in mice. To comprehend the possible mechanism of CEO@NE, an analysis was conducted to ascertain the production of intracellular reactive oxygen species (ROS) in C. albicans . Results: CEO@NE, with the droplet size less than 100 nm and robust storage stability for up to 8 weeks, exhibited comparable anti- Candida activity with CEO. CEO@NE at the concentration lower than 400 μg/mL had no cytotoxic and immunomodulatory effects on murine splenocytes. Intravaginal treatment of CEO@NE (400 μg/mL, 20 μL/day/mouse for 5 consecutive days) curbed Candida colonization, ameliorated histopathological changes, and suppressed inflammatory cytokine production in mice intravaginally challenged with C. albicans . Notably, this treatment preserved the density of vaginal lactic acid bacteria (LAB) crucial for vaginal health. Co-culturing C. albicans with CEO@NE revealed concentration-dependent augmentation of intracellular ROS generation and ensuing cell death. In addition, co-culturing LPS-stimulated murine splenocytes with CEO@NE yielded a decrease in the generation of cytokines. Conclusion: This discovery provides insight into the conceivable antifungal and anti-inflammatory mechanisms of CEO@NE to tackle Candida vaginitis. CEO@NE offers a promising avenue to address the limitations of current treatments, providing novel strategy for treating Candida vaginitis. Keywords: anti-inflammation, Candida vaginitis, cinnamon essential oil, nanoemulsion, reactive oxygen species