Dual-action of clotrimazole loaded - nanosponges vaginal gel for spermicidal action and treatment of vaginal candidiasis: Optimization, in-vitro, ex-vivo, and in-vivo experiments

Clotrimazole (CLO) is a strong antifungal drug approved to treat vaginal candidiasis (VC). Nanosponges (NSs) were developed to maintain providing CLO in a steady pattern with amplified accumulation in the vaginal mucosa. The quasi-emulsion solvent diffusion method was utilized to prepare NSs. The optimized NSs selected by Design Expert® exhibited a production yield percent (PY%) of 60.10 ± 0.39 %, encapsulation efficiency percent (EE%) of 91.21 ± 0.59 %, particle size (PS) 275.50 ± 0.97 nm, polydispersity index (PDI) 0.425 ± 0.01, and zeta potential (ZP) of -27.40 ± 0.25 mV. The morphological results confirmed a spongy, porous structure. Fourier Transform Infrared Spectroscopy ensured the drug encapsulation. Differential scanning calorimetric studies showed no interaction between the excipients and CLO. The prepared NSs-loaded gel of optimized CLO-NSs was evaluated, the mucoadhesive strength (6065.85 ± 52.03 dyne/cm²) with spermicidal activity of (0 % sperm motility/60 s). The ex-vivo deposition depicted significantly increased vaginal retention of CLO by 2.44-fold compared to Candistan® 2 % vaginal cream (the market product). Finally, the in-vivo study on rats demonstrated thesuperior efficacy of CLO-NSs gel relative to Candestan®, with significantly reduced inflammatory biomarkers and minimal histopathological alterations in the treatment of vaginal candidiasis with a high safety profile.