Painting blood vessels and atherosclerotic plaques with an adhesive drug depot

Christian J. Kastrup, Matthias Nahrendorf, Jose Luiz Figueiredo, Haeshin Lee, Swetha Kambhampati, Timothy Lee, Seung Woo Cho, Rostic Gorbatov, Yoshiko Iwamoto, Tram T. Dang, Partha Dutta, Ju Hun Yeon, Hao Cheng, Christopher D. Pritchard, Arturo J. Vegas, Cory D. Siegel, Samantha MacDougall, Michael Okonkwo, Anh Thai, James R. StoneArthur J. Coury, Ralph Weissleder, Robert Langer, Daniel G. Anderson

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83 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)21444-21449
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number52
DOIs
Publication statusPublished - 2012 Dec 26

All Science Journal Classification (ASJC) codes

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    Kastrup, C. J., Nahrendorf, M., Figueiredo, J. L., Lee, H., Kambhampati, S., Lee, T., Cho, S. W., Gorbatov, R., Iwamoto, Y., Dang, T. T., Dutta, P., Yeon, J. H., Cheng, H., Pritchard, C. D., Vegas, A. J., Siegel, C. D., MacDougall, S., Okonkwo, M., Thai, A., ... Anderson, D. G. (2012). Painting blood vessels and atherosclerotic plaques with an adhesive drug depot. Proceedings of the National Academy of Sciences of the United States of America, 109(52), 21444-21449. https://doi.org/10.1073/pnas.1217972110