In Silico Guided Nanoformulation Strategy for Circumvention of Candida albicans Biofilm for Effective Therapy of Candidal Vulvovaginitis

Candidal vulvovaginitis involving multispecies of Candida and epithelium-bound biofilm poses a drug-resistant pharmacotherapeutic challenge. The present study aims for a disease-specific predominant causative organism resolution for the development of a tailored vaginal drug delivery system. The proposed work fabricates a luliconazole-loaded nanostructured lipid carrier-based transvaginal gel for combating Candida albicans biofilm and disease amelioration. The interaction and binding affinity of luliconazole against the proteins of C. albicans and biofilm were assessed using in silico tools. A systematic QbD analysis was followed to prepare the proposed nanogel using a modified melt emulsification-ultrasonication-gelling method. The DoE optimiza-tion was logically implemented to ascertain the effect of independent process variables (excipients concentration; sonication time) on dependent formulation responses (particle size; polydispersity index; entrapment efficiency). The optimized formulation was characterized for final product suitability. The surface morphology and dimensions were spherical and <= 300 nm, respectively. The flow behavior of an optimized nanogel (semisolid) was non-Newtonian similar to marketed preparation. The texture pattern of a nanogel was firm, consistent, and cohesive. The release kinetic model followed was Higuchi (nanogel) with a % cumulative drug release of 83.97 +/- 0.69% in 48 h. The % cumulative drug permeated across a goat vaginal membrane was found to be 53.148 +/- 0.62% in 8 h. The skin-safety profile was examined using a vaginal irritation model (in vivo) and histological assessments. The drug and proposed formulation(s) were checked against the pathogenic strains of C. albicans (vaginal clinical isolates) and in vitro established biofilms. The visualization of biofilms was done under a fluorescence microscope revealing mature, inhibited, and eradicated biofilm structures.

Automated summary

This study aims to develop a tailored vaginal drug delivery system for the treatment of drug-resistant Candida vulvovaginitis involving multispecies of Candida and epithelium-bound biofilm. A luliconazole-loaded nanostructured lipid carrier-based transvaginal gel was fabricated to combat Candida albicans biofilm and alleviate the disease. In silico tools were used to assess the interaction and binding affinity of luliconazole against C. albicans proteins and biofilm. The optimized nanogel formulation showed suitable characteristics, such as small particle size, non-Newtonian flow behavior, and high drug release and permeation rates.