title: Injectable nano-network for glucose-mediated insulin delivery.
abstract: Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial "closed-loop" system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivo studies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered with a degradable nano-network. A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days.
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors: Zhen
authors: Z
authors: Gu
authors: Alex A
authors: AA
authors: Aimetti
authors: Qun
authors: Q
authors: Wang
authors: Tram T
authors: TT
authors: Dang
authors: Yunlong
authors: Y
authors: Zhang
authors: Omid
authors: O
authors: Veiseh
authors: Hao
authors: H
authors: Cheng
authors: Robert S
authors: RS
authors: Langer
authors: Daniel G
authors: DG
authors: Anderson
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007267:Injections; D007328:Insulin / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D003911:Dextrans; D004337:Drug Carriers; D006603:Hexuronic Acids; D007328:Insulin; D020723:Glucuronic Acid; D048271:Chitosan; D005947:Glucose
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