Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 22, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.nano.2019.102091
Keywords
Eudragit (R) L100-55 oral delivery system; Gelatin nanoparticles; DMT1 siRNA; Iron overload; Divalent metal transporter 1
Funding
- National Institute of Biomedical Imaging and Bioengineering, National Institute of Health, USA [EB023025]
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Iron is a nutrient metal, but excess iron promotes tissue damage. Since iron chelation therapies exhibit multiple off-target toxicities, there is a substantial demand for more specific approaches to decrease iron burden in iron overload. While the divalent metal transporter 1 (DMT1) plays a well-established role in the absorption of dietary iron, up-regulation of intestinal DMT1 is associated with iron overload in both humans and rodents. Hence, we developed a novel pH-sensitive multi-compartmental particulate (MCP) oral delivery system that encapsulates DMT1 siRNA and validated its efficacy in mice. Using the gelatin NPs coated with Eudragit (R) L100-55, we demonstrated that DMT1 siRNA-loaded MCPs down-regulated DMT1 mRNA levels in the duodenum, which was consistent with decreased intestinal absorption of orally-administered 59Fe. Together, the Eudragit (R) L100-55-based oral siRNA delivery system could provide an effective strategy to specifically down-regulate duodenal DMT1 and mitigate iron absorption. (C) 2019 Elsevier Inc. All rights reserved.
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