Development of melatonin loaded pectin nanoparticles for the treatment of inflammatory bowel disease: In vitro and in vivo studies

Abstract

Inflammatory bowel disease (IBD) is a general term including long-term inflammatory disorders of all or some parts of the digestive system. Nanoparticles (NPs) can accumulate in the inflamed zone independently of the polymers’ mucoadhesive character.The aim of this study was to prepare and investigate the melatonin loaded pectin-based nanoparticles for Inflammatory Bowel Disease (IBD). Melatonin (MEL) was loaded into nanoparticle system with a modified ionotropic-gelation method. In vitro characterization studies of the nanoparticles were carried out.The effectiveness of the oral and intracolonically administered nanoparticles were investigated in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats. The indicators of oxidative stress and inflammation in the colonic tissue like nitric oxide, malondialdehyde, glutathione, tumor necrosis factor-alpha, Interleukin (IL)-10, and IL-17 levels were investigated. In addition, the histological evaluation was performed.The mean diameter, zeta potential and polydispersity index values of the obtained nanoparticles were 75.3 ± 3.3 nm, 24.24 ± 1.03 mV and 0.109 ± 0.067, respectively. The in vitro drug release studies showed that 84.0 ± 0.7% of the drug was released from the nanoparticles for 8 h. MEL-loaded pectin nanoparticles ameliorated the TNBS-induced colitis. Treatment of the melatonin decreased the damage score by 73.2% in oral and by 67.1% in intracolonic route, respectively. A meaningful decrease was observed in colonic fibrosis, oxidative stress, and inflammatory parameters of the colon accompanying histologic injury. The results of the experiments and histological data showed that MEL-loaded calcium pectinate nanoparticle may be a promising alternative in colonic tissue damage which develops due to oxidative stress in IBD.