Beta-cyclodextrin-based Miconazole Nitrate Nanogel for Vaginal Delivery

A BSTRACT Introduction: Beta cyclodextrin (β-CD) based nanogel was prepared for vaginal delivery to increase the solubility and dissolution profile of miconazole nitrate (MN) to enhance antifungal activity. Methods: MN molecular docking studies were carried out to find the best fit with cyclodextrins. Phase solubility studies were carried out in simulated vaginal fluid (SVF) and distilled water. Furthermore, solubility studies of the pure drug and selected nanogel batch were tested in distilled water and SVF at different pH. A simultaneous crosslinking emulsion solvent evaporation method was used to synthesize the nanogel, where ethylene glycol diglycidyl ether was used as a cross-linker with 20% (w/w) hydroxypropyl methylcellulose as aqueous phase and Span 80 (0, 0.5, 1 or 2%, w/v) and dichloromethane as organic phase. Drug-unloaded and loaded nanogels were further evaluated for percentage yield, swelling ratio, particle size, polydispersity index, and zeta potential. fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy studies were carried out for the selected batch of nanogel. Results: Docking studies revealed the best fit with β-CD, with a maximum glide score of-4.1 kcal/mol and a bond length of 2.6. Phase solubility studies confirmed 1:1 complex formation between MN and β-CD (K = 581.63 M-1). The solubility of MN in nanogel was observed to increase by 0.723-fold in SVF and 0.0879-fold in water. Dissolution studies showed 80.10% drug release at the end of 6 h, compared to the carbopol gel formulation of the drug at 45% only. Furthermore, the antifungal study result showed the highest zone of inhibition compared to the pure drug. Conclusion: Thus, it can be concluded that the β-CD-based nanogel of MN shows promise in enhanced solubility, dissolution, and antifungal activity.