Site-specific intestinal DMT1 silencing to mitigate iron absorption using pH-sensitive multi-compartmental nanoparticulate oral delivery system

We report a novel pH-sensitive multi-compartmental nanoparticulate (MCP) oral delivery system that encapsulates siRNA for silencing the divalent metal transporter 1 (DMT1) gene, a primary iron transporter highly expressed in the intestine. The gelatin nanoparticles-coated with Eudragit® L100–55 are able to protect siRNA from intracellular degradation and allow for sustained release of siRNA in the cytosol. When orally-administered, Eudragit® L100–55 based MCPs containing DMT1 siRNA/gelatin NPs specifically and significantly decreased the expression of DMT1 mRNA in the duodenum, which consequently decreased intestinal absorption of iron. Overall, the oral gene silencing strategy provides a selective and effective method to mitigate intestinal uptake of dietary iron and thereby reduces iron-induced organ dysfunction in individuals with iron overload disorders.
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research