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Site-specific intestinal DMT1 silencing to mitigate iron absorption using pH-sensitive multi-compartmental nanoparticulate oral delivery system.
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2019-10-15 , DOI: 10.1016/j.nano.2019.102091 Yingfang Fan 1 , Harkiranpreet Kaur Dhaliwal 1 , Archita Venugopal Menon 1 , JuOae Chang 1 , Jee Eun Choi 1 , Mansoor M Amiji 1 , Jonghan Kim 1
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2019-10-15 , DOI: 10.1016/j.nano.2019.102091 Yingfang Fan 1 , Harkiranpreet Kaur Dhaliwal 1 , Archita Venugopal Menon 1 , JuOae Chang 1 , Jee Eun Choi 1 , Mansoor M Amiji 1 , Jonghan Kim 1
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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® 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® L100-55-based oral siRNA delivery system could provide an effective strategy to specifically down-regulate duodenal DMT1 and mitigate iron absorption.
中文翻译：
使用pH敏感的多隔室纳米颗粒口服给药系统，可降低肠道特定部位的DMT1沉默，从而减轻铁的吸收。
铁是一种营养金属，但是过量的铁会促进组织损伤。由于铁螯合疗法表现出多种脱靶毒性，因此迫切需要更具体的方法来减少铁超负荷中的铁负荷。尽管二价金属转运蛋白1（DMT1）在膳食铁的吸收中起着公认的作用，但肠道DMT1的上调与人类和啮齿动物中的铁超载有关。因此，我们开发了一种新型的pH敏感的多隔室微粒（MCP）口服递送系统，该系统封装了DMT1 siRNA并验证了其在小鼠中的功效。使用涂有Eudragit®L100-55的明胶NP，我们证明了DMT1 siRNA加载的MCP下调了十二指肠中DMT1 mRNA的水平，这与口服59Fe的肠道吸收减少是一致的。一起，
更新日期：2019-10-15
中文翻译：
使用pH敏感的多隔室纳米颗粒口服给药系统，可降低肠道特定部位的DMT1沉默，从而减轻铁的吸收。
铁是一种营养金属，但是过量的铁会促进组织损伤。由于铁螯合疗法表现出多种脱靶毒性，因此迫切需要更具体的方法来减少铁超负荷中的铁负荷。尽管二价金属转运蛋白1（DMT1）在膳食铁的吸收中起着公认的作用，但肠道DMT1的上调与人类和啮齿动物中的铁超载有关。因此，我们开发了一种新型的pH敏感的多隔室微粒（MCP）口服递送系统，该系统封装了DMT1 siRNA并验证了其在小鼠中的功效。使用涂有Eudragit®L100-55的明胶NP，我们证明了DMT1 siRNA加载的MCP下调了十二指肠中DMT1 mRNA的水平，这与口服59Fe的肠道吸收减少是一致的。一起，
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