A Fungistatic Strategy Using a Shear-Thinning pH-Responsive CMCS-OHA-Lp/Lr Hydrogel for Vulvovaginal Candidiasis

<b>Background</b>: Vulvar vaginal candidiasis (VVC) is a type of vaginitis resulting from a Candida infection of the vaginal mucosa. Traditional treatments using antibiotics often lead to resistance and disrupt the vaginal microenvironment, causing ongoing problems for patients. In response to these challenges, this study introduces a multifunctional intelligent responsive probiotic hydrogel designed to modulate the vaginal microecological environment to combat <i>Candida albicans</i> infection. <b>Methods</b>: The innovative CMCS-OHA-Lp/Lr hydrogel was formulated using oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS) as carriers, incorporating <i>Lactobacillus plantarum</i> (Lp) and <i>Lactobacillus rhamnosus</i> (Lr) as active components. Comprehensive characterization of the CMCS-OHA-Lp/Lr hydrogel revealed its chemical structure, rheological properties, rapid self-healing properties, gel degradation, and the release of lactobacilli in vitro. <b>Results</b>: The findings demonstrated that the hydrogel's cross-linking conferred significant physical properties. In addition, the in vitro release study of Lactobacillus showed that the cumulative release rates of Lp and Lr in the medium with pH 5.5 were 83.50 ± 2.70% and 73.31 ± 2.22%, which proved the pH-responsive release characteristics of probiotics in acidic vaginal environments. Furthermore, the storage activity of Lactobacillus indicated that the survival rates of the CMCS-OHA-Lp and CMCS-OHA-Lr hydrogels were 86.90 ± 0.20% and 85.50 ± 0.56%, respectively, proving that encapsulation within the hydrogels significantly enhanced the storage stability of probiotics. In vivo studies further confirmed that the hydrogel alleviated vulval edema symptoms and reduced <i>C. albicans</i> colonies in the vagina, thereby mitigating vaginal inflammation. <b>Conclusions</b>: In conclusion, this pH-responsive, self-healing, and shear-thinning hydrogel offers a promising approach for the clinical treatment of VVC and serves as an effective probiotic delivery vehicle.