title: Triggered drug release from dynamic microspheres via a protein conformational change.
abstract: In this study we formed and characterized dynamic hydrogel microspheres in which a protein conformational change was used to control microsphere volume changes and the release of an encapsulated drug. In particular, a specific biochemical ligand, trifluoperazine, induced calmodulin's nanometer scale conformation change, which translated to a 48.7% microsphere volume decrease. This specific, ligand-induced volume change triggered the release of a model drug, vascular endothelial growth factor (VEGF), at pre-determined times. After release from the microspheres, 85.6 +/- 10.5% of VEGF was in its native conformation. Taken together, these results suggest that protein conformational change could serve as a useful mechanism to control drug release from dynamic hydrogels.
authors.affiliation: wlmurphy@wisc.edu
authors.forename: William J
authors.initials: WJ
authors.lastname: King
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Pytel
authors.forename: Kelvin
authors.initials: K
authors.lastname: Ng
authors.forename: William L
authors.initials: WL
authors.lastname: Murphy
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000627:therapeutic use*; D008863:Microspheres; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D011506:Proteins; D042461:Vascular Endothelial Growth Factor A