In vitro/in vivo evaluation of nanoparticular systems in inflammatory bowel disease model

The aim of this study was to formulate colon targetted nanoparticular drug carrier systems of melatonin, characterization of them, conducting in vitro release studies of the prepared formulations and to determine the effect of the formulation which was found to be suitable as a result of artifical neural network modelling, on TNBS induced colitis in rats.Melatonin loaded calcium pectinate nanoparticle formulations prepared with modified ionotropic gelation method. Prepared nanoparticle formulations characterized by particle size, zeta potential and polydispersity index, the in vitro release studies were performed and mucoadhesion were investigated.AFM and TEM techniques are used to obtain nanoparticle images.The formulation which was found to be suitable as a result of artifical neural network modelling was used in in vivo studies.Wistar male rats were used in in vivo studies. 10 mg/kg melatonin loaded nanoparticle formulation was given oral and intracolonic route to TNBS induced colitis rats for four days. The obtained results are compared with the results of the rats which was given blank nanoparticle formulation.At the end of the treatment, oxidative parameters (NOx, MDA ve GSH) of the colonic tissue and cytokine levels was evaluated. Colonic tissue NOx and MDA levels in the group treated with melatonin by oral and intracolonic route were found to be lower compared to the groups which treated with blank nanoparticle formulation. Colonic tissue GSH levels in the group treated with melatonin by oral and intracolonic route were found to be higher compared to the groups which treated with blank nanoparticle formulation. Also proinflammatory TNF-?, IL-17 levels and antiinflammatory IL-10 levels in the group treated with melatonin by oral and intracolonic route were found to be lower compared to the groups which treated with blank nanoparticle formulation.According to histological findings, the tissue healing in the group treated with melatonin loaded nanoparticle formulation by oral and intracolonic route was found better than the group treated with blank nanoparticle formulation.The results of the experiments showed that, melatonin loaded nanoparticle formulation can be effective in colonic tissue damage which develops due to oxidative stress in IBD.