Thermosensitive hydrogels for vaginal delivery of secnidazole as an approach to overcome the systemic side-effects of oral preparations

Abstract

Secnidazole (SEC) has been suggested as an alternative agent against Trichomonas vaginalis to overcome the adverse effects, antimicrobial resistance problems and poor adherence to the currently available therapy. Once no topical formulation may be found in the market until now, SEC was incorporated in thermosensitive bioadhesive systems to extend the contact time in the mucosa and to avoid a systemic drug disposition. Formulations containing 20% poloxamer 407, 1% poloxamer 188 and 1 or 2.5% chitosan showed suitable sol-gel transition temperature (> 30 °C), presenting a fast gelation time (100-115 s). Rheological, dynamic light scattering and infrared spectroscopy analysis suggested molecular interactions among polymers. Chitosan increased the mucoadhesion strength of the formulations. In addition, hydrogels showed a tendency to decrease the drug transport rate through mucosa when compared to the control. Mucin was also added onto mucosa for a more realistic simulation of permeability/retention. In the presence of this agent, hydrogels containing chitosan reduced the permeability/retention of the drug in approximately 2.0-fold when compared to the control. Therefore, the hydrogels presented suitable characteristics to remain in the vaginal environment, which would result in effective local treatment of trichomoniasis.