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- Development of a vaginal gel to treat intra- epithelial lesions caused by HPVPublication . Rosado, Beatriz Ferreira; Cruz, Carla Patricia Alves Freire Madeira daCervical cancer is one of the most frequent cancers and the treatment options are limited and invasive, with a survival rate of about 50%. Human Papillomavirus (HPV) is a DNA virus responsible for the majority of cervical cancer and contributes to 610,000 new cases per year. Many studies have been conducted to improve treatment options for cervical HPV-related lesions. Vaginal gel formulations are a topical dosage form for drug delivery and previous studies have shown that Thymus vulgaris essential oil (TEO) presented anticancer properties, being a promising component to be included in new therapeutic approaches. This study focuses on using TEO-combined formulations with lipidic nanoparticles with Imiquimod and functionalized with a DNA aptamer, AT11, to improve the selectivity for cervical cancer cells. TEO-combined formulations were prepared based on the universal placebo for vaginal gels and later combined with AT11-guided nanoparticles associated with Imiquimod. They were characterized in terms of pH, viscosity, osmolality, and buffering capacity. Their biological effect was assessed via cell viability assays, as well as the cellular uptake of the formulations via confocal microscopy using MTT in HeLa, SiHa, CaSki, and NHDF cell lines. Finally, it was determined the susceptibility of infectious microorganisms (namely Candida albicans, Aspergillus brasiliensis, and Staphylococcus aureus) to the formulations. Formulations’ characterization demonstrated that the physicochemical properties are adequate for vaginal drug delivery, overcoming issues like leakage, possible irritation, and low retention in the vaginal canal. It was observed a cytotoxic effect of the AT11- guided liposomes associated with Imiquimod in the presence of TEO in cancer cells but not in healthy cell lines. These results suggest that TEO can potentiate the cytotoxic effect of Imiquimod-associated liposomes, and AT11 improves their selectivity to cervical cancer cells. Cellular uptake showed that the formulations were well internalized by the cells in the study and antimicrobial studies showed growth inhibition in higher formulations’ concentrations. Overall, the results suggest that the developed formulation represents a promising topical approach to treat cervical lesions caused by HPV.