title: Glucose-Triggered Insulin Release from Fe3+-Cross-linked Alginate Hydrogel: Experimental Study and Theoretical Modeling.
abstract: We study the mechanisms involved in the release, triggered by the application of glucose, of insulin entrapped in Fe3+-cross-linked alginate hydrogel particles further stabilized with a polyelectrolyte. Platelet-shaped alginate particles are synthesized containing enzyme glucose oxidase conjugated with silica nanoparticles, which are also entrapped in the hydrogel. Glucose diffuses in from solution, and production of hydrogen peroxide is catalyzed by the enzyme within the hydrogel. We argue that, specifically for the Fe3+-cross-linked systems, the produced hydrogen peroxide is further converted to free radicals via a Fenton-type reaction catalyzed by the iron cations. The activity of free radicals, as well as the reduction of Fe3+by the enzyme, and other mechanisms contribute to the decrease in density of the hydrogel. As a result, while the particles remain intact, void sizes increase and release of insulin ensues and is followed experimentally. A theoretical description of the involved processes is proposed and utilized to fit the data. It is then used to study the long-time properties of the release process that offers a model for designing new drug-release systems.
authors.affiliation: Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, 13699-5810, USA.|Institute of Nano- and Biotechnologies, FH Aachen, Aachen University of Applied Sciences, Campus Jülich, Heinrich-Mußmann-Str. 1, 52428, Jülich, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Scheja
authors.affiliation: Department of Physics, Clarkson University, Potsdam, NY, 13699-5820, USA.
authors.forename: Sergii
authors.identifier: http://orcid.org/0000-0002-6847-6019
authors.initials: S
authors.lastname: Domanskyi
authors.affiliation: Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, 13699-5810, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Gamella
authors.affiliation: Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, 13699-5810, USA.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Wormwood
authors.affiliation: Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, 13699-5810, USA.
authors.forename: Costel C
authors.initials: CC
authors.lastname: Darie
authors.affiliation: Institute of Nano- and Biotechnologies, FH Aachen, Aachen University of Applied Sciences, Campus Jülich, Heinrich-Mußmann-Str. 1, 52428, Jülich, Germany.|Peter Grünberg Institute (PGI-8), Research Centre Jülich GmbH, 52425, Jülich, Germany.
authors.forename: Arshak
authors.initials: A
authors.lastname: Poghossian
authors.affiliation: Institute of Nano- and Biotechnologies, FH Aachen, Aachen University of Applied Sciences, Campus Jülich, Heinrich-Mußmann-Str. 1, 52428, Jülich, Germany.|Peter Grünberg Institute (PGI-8), Research Centre Jülich GmbH, 52425, Jülich, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schöning
authors.affiliation: Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, 13699-5810, USA.
authors.forename: Artem
authors.initials: A
authors.lastname: Melman
authors.affiliation: Department of Physics, Clarkson University, Potsdam, NY, 13699-5820, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Privman
authors.affiliation: Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, 13699-5810, USA.
authors.forename: Evgeny
authors.identifier: http://orcid.org/0000-0002-1618-4620
authors.initials: E
authors.lastname: Katz
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism*; D005947:Glucose / Q000737:chemistry / Q000378:metabolism*; D005949:Glucose Oxidase / Q000737:chemistry / Q000378:metabolism*; D020100:Hydrogels / Q000737:chemistry / Q000378:metabolism*; D007328:Insulin / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D005290:Ferric Compounds; D020100:Hydrogels; D007328:Insulin; D012822:Silicon Dioxide; D005949:Glucose Oxidase; D005947:Glucose
keywords: alginate; controlled release; glucose; hydrogen peroxide; insulin