title: H2O2-Responsive Vesicles Integrated with Transcutaneous Patches for Glucose-Mediated Insulin Delivery.
abstract: A self-regulated "smart" insulin administration system would be highly desirable for diabetes management. Here, a glucose-responsive insulin delivery device, which integrates H2O2-responsive polymeric vesicles (PVs) with a transcutaneous microneedle-array patch was prepared to achieve a fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from block copolymer incorporated with polyethylene glycol (PEG) and phenylboronic ester (PBE)-conjugated polyserine (designated mPEG-b-P(Ser-PBE)) and loaded with glucose oxidase (GOx) and insulin. The polymeric vesicles function as both moieties of the glucose sensing element (GOx) and the insulin release actuator to provide basal insulin release as well as promote insulin release in response to hyperglycemic states. In the current study, insulin release responds quickly to elevated glucose and its kinetics can be modulated by adjusting the concentration of GOx loaded into the microneedles. In vivo testing indicates that a single patch can regulate glucose levels effectively with reduced risk of hypoglycemia.
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.|State Key Laboratory of Polymer Chemistry and Physics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Jilin, 130022, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Hu
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: 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.
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.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Medicine, University of North Carolina School of Medicine , Chapel Hill, North Carolina 27599, United States.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Kahkoska
authors.affiliation: State Key Laboratory of Polymer Chemistry and Physics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Jilin, 130022, People's Republic of China.
authors.forename: Zhigang
authors.identifier: 0000-0003-2974-1825
authors.initials: Z
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Polymer Chemistry and Physics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Jilin, 130022, People's Republic of China.
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Medicine, University of North Carolina School of Medicine , 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.|Department of Medicine, University of North Carolina School of Medicine , 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; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005947:Glucose / Q000032:analysis / Q000378:metabolism*; D005949:Glucose Oxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry*; D007003:Hypoglycemia / Q000188:drug therapy*; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D013311:Streptozocin; D057968:Transdermal Patch
chemical_list: D004337:Drug Carriers; D007328:Insulin; D011108:Polymers; D013311:Streptozocin; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D005947:Glucose
keywords: diabetes; drug delivery; glucose-responsive; insulin; polymersome; vesicles