TY - JOUR
T1 - Painting blood vessels and atherosclerotic plaques with an adhesive drug depot
AU - Kastrup, Christian J.
AU - Nahrendorf, Matthias
AU - Figueiredo, Jose Luiz
AU - Lee, Haeshin
AU - Kambhampati, Swetha
AU - Lee, Timothy
AU - Cho, Seung Woo
AU - Gorbatov, Rostic
AU - Iwamoto, Yoshiko
AU - Dang, Tram T.
AU - Dutta, Partha
AU - Yeon, Ju Hun
AU - Cheng, Hao
AU - Pritchard, Christopher D.
AU - Vegas, Arturo J.
AU - Siegel, Cory D.
AU - MacDougall, Samantha
AU - Okonkwo, Michael
AU - Thai, Anh
AU - Stone, James R.
AU - Coury, Arthur J.
AU - Weissleder, Ralph
AU - Langer, Robert
AU - Anderson, Daniel G.
PY - 2012/12/26
Y1 - 2012/12/26
N2 - 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 drugeluting 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.
AB - 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 drugeluting 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.
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U2 - 10.1073/pnas.1217972110
DO - 10.1073/pnas.1217972110
M3 - Article
C2 - 23236189
AN - SCOPUS:84871822549
SN - 0027-8424
VL - 109
SP - 21444
EP - 21449
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 52
ER -