Colon delivery of agomelatine nanoparticles in the treatment of TNBS induced ulcerative colitis.

Agomelatine is an atypical antidepressant with a long half-life and the mechanism of action similar to melatonin. Agomelatine is a strong antioxidant and its anti-inflammatory effect has been reported in many studies. The current study aimed to evaluate the anti-inflammatory effect of agomelatine loaded in targeted nanoparticles (NPs) in an experimental colitis model induced by trinitrobenzene sulfonic acid (TNBS). Poly(1-vinylpyrrolidone)-graft-(1-triacontene) (PVP-TA) and Eudragit®-FS30D polymers were used alone and in combination as time, pH and time/pH dependent formulations respectively. The optimal formula was selected according to their physicochemical properties such as particle size, morphology, and drug release pattern. Six separate groups of rats were induced with 0.5 ml of TNBS. The designed groups were: normal, untreated, agomelatine (25 mg/kg/d), agomelatine/ Eudragit®-FS30D NPs, agomelatine/ Eudragit-FS30D/PVP-TA NPs, and dexamethasone (Dex., 1 mg/kg/d). Twenty-four hours after the last administration, colonic tissue was analyzed for macroscopic and histopathological evaluations, along with quantification of malondialdehyde (MDA) and myeloperoxidase (MPO) levels. The results showed that the PVP-TA NPs alone was not suitable regarding to release profile and particle size distribution. However, Eudragit-FS30D NPs alone and Eudragit-FS30D + PVP-TA NPs passed physicochemical evaluations and were both effective in reducing the symptoms and indices of experimental colitis. Taken together, targeted NPs of agomelatine are potentially effective in treatment of ulcerative colitis.