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Stabilization of Glucagon by Trehalose Glycopolymer Nanogels
Author(s) -
Boehnke Natalie,
Kammeyer Jacquelin K.,
Damoiseaux Robert,
Maynard Heather D.
Publication year - 2018
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201705475
Subject(s) - nanogel , trehalose , glucagon , glycopolymer , methacrylate , copolymer , materials science , dynamic light scattering , chemistry , combinatorial chemistry , polymer chemistry , biochemistry , organic chemistry , polymer , drug delivery , nanotechnology , nanoparticle , hormone
Glucagon is a peptide hormone used for the treatment of hypoglycemia; however, its clinical potential is limited by its insolubility and instability in solution. Herein, the encapsulation, stabilization, and release of glucagon by trehalose glycopolymer nanogels are reported. Methacrylate‐functionalized trehalose is copolymerized with pyridyl disulfide ethyl methacrylate using free radical polymerization conditions to form trehalose glycopolymers with thiol‐reactive handles. Glucagon is chemically modified to contain two thiol groups and is subsequently utilized as the cross‐linker to form redox‐responsive trehalose nanogels with greater than 80% conjugation yield. Nanogel formation and subsequent glucagon stabilization are characterized using polyacrylamide gel electrophoresis, dynamic light scattering, and transmission electron microscopy. It is determined that the solution stability of the glucagon increased from less than 24 h to at least three weeks in the nanogel form. Additionally, in vitro activity of the synthesized glucagon analog and released glucagon is investigated, demonstrating that the glucagon remains active after modification. It is anticipated that these glucagon–nanogel conjugates will be useful as a stabilizing glucagon formulation, allowing for cargo release under mild reducing conditions.