title: In vitro and in vivo testing of glucose-responsive insulin-delivery microdevices in diabetic rats.
abstract: We have developed glucose-responsive implantable microdevices for closed-loop delivery of insulin and conducted in vivo testing of these devices in diabetic rats. The microdevices consist of an albumin-based bioinorganic membrane that utilizes glucose oxidase (GOx), catalase (CAT) and manganese dioxide (MnO(2)) nanoparticles to convert a change in the environmental glucose level to a pH stimulus, which regulates the volume of pH-sensitive hydrogel nanoparticles and thereby the permeability of the membrane. The membrane is integrated with microfabricated PDMS (polydimethylsiloxane) structures to form compact, stand-alone microdevices, which do not require tethering wires or tubes. During in vitro testing, the microdevices showed glucose-responsive insulin release over multiple cycles at clinically relevant glucose concentrations. In vivo, the microdevices were able to counter hyperglycemia in diabetic rats over a one-week period. The in vitro and in vivo testing results demonstrated the efficacy of closed-loop biosensing and rapid response of the 'smart' insulin delivery devices.
authors.affiliation: Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael K L
authors.initials: MK
authors.lastname: Chu
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Gordijo
authors.forename: Simon
authors.initials: S
authors.lastname: Chiang
authors.forename: Alexander
authors.initials: A
authors.lastname: Ivovic
authors.forename: Khajag
authors.initials: K
authors.lastname: Koulajian
authors.forename: Adria
authors.initials: A
authors.lastname: Giacca
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D002374:Catalase / Q000737:chemistry / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism; D005949:Glucose Oxidase / Q000737:chemistry / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage*; D017895:Manganese Compounds / Q000737:chemistry; D008567:Membranes, Artificial; D053768:Metal Nanoparticles / Q000737:chemistry; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D010087:Oxides / Q000737:chemistry; D051381:Rats; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism
chemical_list: D004129:Dimethylpolysiloxanes; D004337:Drug Carriers; D007328:Insulin; D017895:Manganese Compounds; D008567:Membranes, Artificial; D010087:Oxides; D012709:Serum Albumin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C013830:baysilon; D005949:Glucose Oxidase; D002374:Catalase; D005947:Glucose; C016552:manganese dioxide