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

Abstract

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 optimization 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.

In silico and in vitro assessment of an optimized QbD-guided myoinositol and metformin-loaded mucus-penetrating particle-based gel for the amelioration of PCOS

“…For the intravaginal drug delivery system, the permeation of drug/MPPs across the mucosal vaginal barriers was demonstrated to be a critical factor, which should presumably maintain a minimum effective concentration of therapeutic drug at the ovarian tissue while being inserted through the uterovaginal pathway. 14 The present study was conducted on the vaginal mucosa tissue of a goat to determine the penetration depth and intensity of MPPs and MPPs-gel, which were compared with the conventional gel. The prepared slides of the sample were analysed under a confocal microscope.…”

“…This experiment was continued for approximately 6 h, which was expected to be sufficient time for the diffusion of the dye across the tissue. 14 …”

“…To better understand the binding mode of MTF and MI (ligand molecules) at the molecular level, we carried out molecular docking simulations of the two compounds at the insulin and inositol receptor catalytic ligand binding sites (PDB ID: 1ir3 and 3uj4), respectively. 14 The 3-dimensional (3D) ligands were stretched and transferred to the mol-sd le, and then entered into the LigPrep module for the docking study at the molecular level through the LigPrep method. Apo-proteins and the receptor grid were taken from the RCSB protein data bank, which was developed by removing the solvent by inserting a hydrogen molecule and diminishing the energy using the protein development wizard panel.…”

Nanogel-based composites for bacterial antibiofilm activity: advances, challenges, and prospects

“…In addressing vulvovaginal candidiasis, a nanostructured lipid carrier-based transvaginal gel loaded with luliconazole showed promising results against Candida albicans biofilms. 82 Moreover, biofunctionalized nanosilver (ICS-Ag) using itaconyl-chondroitin sulfate nanogel (ICSNG) effectively combated microbial infections on medical devices. ICS-Ag demonstrated that it damaged the bacterial cell membrane, resulting in the release of internal cell contents and causing bacterial death.…”