title: Hypoxia and H2O2Dual-Sensitive Vesicles for Enhanced Glucose-Responsive Insulin Delivery.
abstract: A glucose-responsive closed-loop insulin delivery system mimicking pancreas activity without long-term side effect has the potential to improve diabetic patients' health and quality of life. Here, we developed a novel glucose-responsive insulin delivery device using a painless microneedle-array patch containing insulin-loaded vesicles. Formed by self-assembly of hypoxia and H2O2dual-sensitive diblock copolymer, the glucose-responsive polymersome-based vesicles (d-GRPs) can disassociate and subsequently release insulin triggered by H2O2and hypoxia generated during glucose oxidation catalyzed by glucose specific enzyme. Moreover, the d-GRPs were able to eliminate the excess H2O2, which may lead to free radical-induced damage to skin tissue during the long-term usage and reduce the activity of GOx. In vivo experiments indicated that this smart insulin patch could efficiently regulate the blood glucose in the chemically induced type 1 diabetic mice for 10 h.
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.|Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Yu
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.|Department of Polymer Science & Engineering and Key Laboratory of High Performance Polymer Materials & Technology of MOE, School of Chemistry & Chemical Engineering, Nanjing University , Nanjing, 210023, China.
authors.forename: Chenggen
authors.initials: C
authors.lastname: Qian
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.|Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Mechanical and Aerospace Engineering, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.|Department of Mechanical and Aerospace Engineering, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Polymer Science & Engineering and Key Laboratory of High Performance Polymer Materials & Technology of MOE, School of Chemistry & Chemical Engineering, Nanjing University , Nanjing, 210023, China.
authors.forename: Qundong
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Frances S
authors.initials: FS
authors.lastname: Ligler
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.|Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.|Department of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Zhen
authors.identifier: 0000-0003-2947-4456
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015687:Cell Hypoxia; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005947:Glucose / Q000378:metabolism*; D005949:Glucose Oxidase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008810:Mice, Inbred C57BL; D009593:Nitroimidazoles / Q000737:chemistry; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D009593:Nitroimidazoles; D010455:Peptides; C027794:polyserine; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D005947:Glucose
keywords: Drug delivery; H2O2-sensitive; diabetes; glucose-responsive; hypoxia-sensitive; insulin