Desenvolvimento de nanoemulsões de óleo de romã contendo ou não cetoprofeno: avaliação da atividade antitumoral e antinociceptiva

Abstract

This study aimed to prepare nanoemulsions of pomegranate seed oil, containing or not ketoprofen, and to evaluate antitumor and antinociceptive activity. First, pomegranate seed oil nanoemulsions were prepared by spontaneous emulsification method and two oil concentrations were tested. The formulations were evaluated for physical stability, antioxidant activity by DPPH method and antitumor activity against C6 glioma cell line. After physical stability studies formulations presented suitable physicochemical characteristics and were stable against sedimentation and phase separation. In relation to the antioxidant activity, the formulations kept the activity of pomegranate seed oil at different concentrations. Nanoemulsions and pomegranate seed oil showed antitumor action against glioma cells and were no toxic to astrocytes. In the second approach, efficacy of the combination of the pomegranate seed oil and ketoprofen incorporated in nanoemulsions was evaluated, as a promising alternative for treating inflammatory pain. The formulations showed adequate physicochemical characteristics after been subjected to mechanical stress and temperature changes. The nanoemulsions were able to protect ketoprofen against UVC degradation and about 100% of the drug was released in 5 hours. In the evaluation of in vivo antinociceptive activity, blank nanoemulsion had effect in 1 h, while nanoemulsion containing ketoprofen during 12 h of pretreatment. In return, the ketoprofen showed effect up to 2 hr of pretreatment. Regarding the dose-response curve, free drug had effect up to a dose of 0.5 mg/Kg, while ketoprofen-loaded nanoemulsion showed effect1.0 mg/Kg. Locomotors parameters were not affected, discarding non specific effects.