Novel nanoparticles for oral insulin delivery via the paracellular pathway

Abstract

Novel nanoparticles (NPs) coated with chitosan which allow insulin to be administeredorally were developed. The NPs could transiently and reversibly open the tight junctions inCaco-2 cell monolayers, thus increasing their paracellular permeability. After oraladministration of the FITC-labelled NPs, fluorescence signals, co-localized with ZO-1proteins, were observed at cell–cell contact sites in the small intestine of rats. The intensityof fluorescence signals observed at the duodenum was stronger and appeared at adeeper level than at the jejunum and the ileum. The insulin-loaded NPs suspendedin water were stable in typical storage conditions. Release of the loaded insulindepended greatly on the stability of the NPs at distinct pH environments. Oraladministration of insulin in the form of NPs in diabetic rats demonstrated asustained effect of decreasing the blood glucose level over at least 10 h, indicating theeffect of the prepared NPs in enhancing the absorption of fully functional insulin.