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
Date
12/14/2012Pubmed ID
23236189Pubmed Central ID
PMC3535589DOI
10.1073/pnas.1217972110Scopus ID
2-s2.0-84871822549 (requires institutional sign-in at Scopus site) 111 CitationsAbstract
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.
Author List
Kastrup CJ, Nahrendorf M, Figueiredo JL, Lee H, Kambhampati S, Lee T, Cho SW, Gorbatov R, Iwamoto Y, Dang TT, Dutta P, Yeon JH, Cheng H, Pritchard CD, Vegas AJ, Siegel CD, MacDougall S, Okonkwo M, Thai A, Stone JR, Coury AJ, Weissleder R, Langer R, Anderson DGAuthor
Christian Kastrup PhD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdhesivenessAdhesives
Animals
Apolipoproteins E
Arteries
Blood Vessels
Catechols
Dexamethasone
Drug Delivery Systems
Female
Gels
Human Umbilical Vein Endothelial Cells
Implants, Experimental
Inflammation
Mice
Mice, Inbred C57BL
Plaque, Atherosclerotic
Solubility
Stress, Mechanical
Stress, Physiological
