Triggered drug release from dynamic microspheres via a protein conformational change.
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.
King
William J
WJ
wlmurphy@wisc.edu
Pytel
Nicholas J
NJ
Ng
Kelvin
K
Murphy
William L
WL
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
D003692:Delayed-Action Preparations; D020100:Hydrogels; D011506:Proteins; D042461:Vascular Endothelial Growth Factor A