Lee, Jung Seok, Han, Patrick, Chaudhury, Rabib, Khan, Shihan, Bickerton, Sean, McHugh, Michael D, Park, Hyun Bong, Siefert, Alyssa L, Rea, Gerald, Carballido, Jose, Horwitz, David A, Criscione, Jason, Perica, Karlo, Samstein, Robert, Rageb, Ragy, Kim, Dongin and Fahmy, Tarek M (2021) Metabolic and immunomodulatory control of type 1 diabetes via orally delivered bile-acid-polymer nanocarriers of insulin or rapamycin. Nature Biomedical Engineering, 2021 (5). pp. 983-997.

Abstract

We describe oral nanocarriers, termed “NanoPills” (NPs), for simultaneous short-term control and long-term reversal of pancreatic inflammation. We hypothesized that since bile acids emulsify fats during digestion, regulate glucose and modulate immunity, that NPs constructed from polymeric bile acid will be effective, multifunctional, oral therapeutics. Polymerized ursodeoxycholic acid (pUDCA) NP protected encapsulated agent in the stomach, permeated intestinal epithelia, then bound macrophage bile receptors with high avidity. Strikingly, pUDCA NPs localized to the pancreas after oral ingestion through macrophage-mediated transport and particle enterohepatic circulation. In a drug-induced pancreatic inflammation model, rapamycin-loaded NPs prevented disease. In a spontaneous model of type I diabetes (T1D), NP alone restored normoglycemia for 2 weeks and reversed disease with loaded insulin. Thus, for the first time, an integrative approach is presented enabling oral delivery through a carrier that intrinsically restores endogenous pancreatic insulin secretion, and tolerogenic immunity for rapid control and long-term regulation of T1D.

Item Type:	Article
Keywords:	Nanoparticles, bile acids, autoimmunity
Date Deposited:	21 Oct 2021 00:45
Last Modified:	21 Oct 2021 00:45
URI:	https://oak.novartis.com/id/eprint/37400