title: Bio-inspired synthetic nanovesicles for glucose-responsive release of insulin.
abstract: A new glucose-responsive formulation for self-regulated insulin delivery was constructed by packing insulin, glucose-specific enzymes into pH-sensitive polymersome-based nanovesicles assembled by a diblock copolymer. Glucose can passively transport across the bilayer membrane of the nanovesicle and be oxidized into gluconic acid by glucose oxidase, thereby causing a decrease in local pH. The acidic microenvironment causes the hydrolysis of the pH sensitive nanovesicle that in turn triggers the release of insulin in a glucose responsive fashion. In vitro studies validated that the release of insulin from nanovesicle was effectively correlated with the external glucose concentration. In vivo experiments, in which diabetic mice were subcutaneously administered with the nanovesicles, demonstrate that a single injection of the developed nanovesicle facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 5 days.
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: Wanyi
authors.initials: W
authors.lastname: Tai
authors.forename: Ran
authors.initials: R
authors.lastname: Mo
authors.forename: Jin
authors.initials: J
authors.lastname: Di
authors.forename: Vinayak
authors.initials: V
authors.lastname: Subramanian
authors.forename: Xiao
authors.initials: X
authors.lastname: Gu
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D005942:Gluconates / Q000737:chemistry; D005947:Glucose / Q000008:administration & dosage* / Q000737:chemistry*; D005949:Glucose Oxidase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D005942:Gluconates; D007328:Insulin; D011108:Polymers; D005949:Glucose Oxidase; D005947:Glucose; C030691:gluconic acid