The Impact of Lactobacillus-Rich Probiotic Nutrition on the Pharmacological Efficacy of Clotrimazole Delivered via Mucoadhesive Thermosensitive Hydrogels in Human Subjects with Recurrent Candidiasis

Abstract

Background: Recurrent vulvovaginal candidiasis (RVVC) is a persistent infectious and inflammatory condition associated with microbial dysbiosis, biofilm-mediated fungal resistance, and impaired mucosal structural integrity. Emerging therapeutic approaches emphasize multi-layered interventions integrating pharmacological delivery systems, microbiome modulation, and tissue regeneration strategies. Objective: This study evaluated the impact of Lactobacillus-rich probiotic nutrition on the pharmacological efficacy of clotrimazole delivered via mucoadhesive thermosensitive hydrogels, with adjunct fractional CO₂ laser therapy in human subjects with recurrent candidiasis. Methods: A randomized comparative clinical design was conducted involving 120 women aged 22–45 years diagnosed with RVVC. Participants were allocated into three groups receiving clotrimazole-loaded mucoadhesive thermosensitive hydrogel therapy alone, hydrogel therapy combined with probiotic nutritional supplementation, or triple therapy including probiotic nutrition and fractional CO₂ laser treatment. Clinical, microbiological, biochemical, and structural outcomes were evaluated over 12 weeks of treatment followed by 6 months of recurrence monitoring. Results: The triple-therapy group demonstrated superior clinical and biochemical outcomes, including significant reduction in vaginal pH, decreased Candida load, and enhanced lactic acid concentration (p < 0.01). Structural assessment revealed marked improvement in vaginal epithelial thickness, moisture retention, and Vaginal Health Index scores (p < 0.001). Scanning electron microscopy confirmed restoration of epithelial surface architecture and minimal fungal biofilm presence in the triple-therapy group. Conclusion: Lactobacillus-rich probiotic nutrition significantly enhances the pharmacological effectiveness of clotrimazole delivered through mucoadhesive thermosensitive hydrogels. The integration of microbiome restoration and fractional CO₂ laser therapy produces synergistic therapeutic effects by targeting fungal eradication, microbial ecological stabilization, and mucosal structural regeneration. Triple-modal intervention represents a promising advanced therapeutic strategy for recurrent vulvovaginal candidiasis; however, large-scale multicenter randomized trials are required to validate long-term safety and clinical efficacy.