Painting blood vessels and atherosclerotic plaques with an adhesive drug depot

Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21444-9. doi: 10.1073/pnas.1217972110. Epub 2012 Dec 11.

Abstract

The treatment of diseased vasculature remains challenging, in part because of the difficulty in implanting drug-eluting devices without subjecting vessels to damaging mechanical forces. Implanting materials using adhesive forces could overcome this challenge, but materials have previously not been shown to durably adhere to intact endothelium under blood flow. Marine mussels secrete strong underwater adhesives that have been mimicked in synthetic systems. Here we develop a drug-eluting bioadhesive gel that can be locally and durably glued onto the inside surface of blood vessels. In a mouse model of atherosclerosis, inflamed plaques treated with steroid-eluting adhesive gels had reduced macrophage content and developed protective fibrous caps covering the plaque core. Treatment also lowered plasma cytokine levels and biomarkers of inflammation in the plaque. The drug-eluting devices developed here provide a general strategy for implanting therapeutics in the vasculature using adhesive forces and could potentially be used to stabilize rupture-prone plaques.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesiveness / drug effects
  • Adhesives / chemistry*
  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / metabolism
  • Arteries / drug effects
  • Arteries / pathology
  • Blood Vessels / drug effects
  • Blood Vessels / pathology*
  • Catechols / chemistry
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use*
  • Drug Delivery Systems
  • Female
  • Gels / chemistry
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Implants, Experimental
  • Inflammation / pathology
  • Mice
  • Mice, Inbred C57BL
  • Plaque, Atherosclerotic / drug therapy*
  • Plaque, Atherosclerotic / pathology*
  • Solubility
  • Stress, Mechanical
  • Stress, Physiological / drug effects

Substances

  • Adhesives
  • Apolipoproteins E
  • Catechols
  • Gels
  • Dexamethasone
  • catechol