Topical loratadine-loaded invasomal gel repurposed for vulvovaginal candidiasis; in vitro, in silico, ex vivo, and in vivo studies.

The current research work explored the anti-inflammatory and antifungal activity of loratadine versus Candida albicans for treating vulvovaginal candidiasis (VVC). Loratadine was incorporated into terpene-enriched nanocarrier invasomes (IVS) using a thin-film hydration approach, where a D-optimal design was employed to investigate the lipid amount, terpene percent and type impact on the entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimal formula was assessed regarding morphology, Fourier transform infrared (FTIR), in silico study, and differential scanning calorimetry (DSC). Subsequently, the optimal formula was incorporated into a gel base and characterized via ex vivo permeation studies. Lastly, in vivo investigations were performed to evaluate the performance of the loratadine-loaded IVS gel. The selected formula was spherical and had EE% of 91.95 ± 1.5 %, PS of 132.81 ± 2.7 nm, PDI of 0.326 ± 0.08, and ZP of -23.42 ± 0.38 mV. The FTIR and DSC studies verified the successful entrapment of the drug, while the in silico study demonstrated the thermodynamic stability of IVS. The IVS gel showed enhancement in drug deposition within vaginal tissues of 3.8 folds compared to free drug gel. Loratadine-loaded IVS gel showed remarkable improvement in eradicating candida infection by suppression of β-D-glucan. Furthermore, the IVS gel showed a significant anti-inflammatory effect reflected by marked suppression of NO, iNOS, COX-2, TNF-α, IL-1B and down-regulation in NF-κB, Src and Syk gene expressions. These results were confirmed via histopathological and immunohistological examinations. This work highlights the potential of loratadine as a promising therapy for VVC.