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. Stone & 4 others Arthur J. Coury, Ralph Weissleder, Robert Langer, Daniel G. Anderson

Research output: Contribution to journalArticle

74 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

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Paintings
Atherosclerotic Plaques
Adhesives
Blood Vessels
Pharmaceutical Preparations
Gels
Equipment and Supplies
Bivalvia
Endothelium
Rupture
Atherosclerosis
Biomarkers
Macrophages
Steroids
Cytokines
Inflammation
Therapeutics

All Science Journal Classification (ASJC) codes

  • General

Cite this

Kastrup, C. J., Nahrendorf, M., Figueiredo, J. L., Lee, H., Kambhampati, S., Lee, T., ... 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
Kastrup, Christian J. ; Nahrendorf, Matthias ; Figueiredo, Jose Luiz ; Lee, Haeshin ; Kambhampati, Swetha ; Lee, Timothy ; Cho, Seung-Woo ; Gorbatov, Rostic ; Iwamoto, Yoshiko ; Dang, Tram T. ; Dutta, Partha ; Yeon, Ju Hun ; Cheng, Hao ; Pritchard, Christopher D. ; Vegas, Arturo J. ; Siegel, Cory D. ; MacDougall, Samantha ; Okonkwo, Michael ; Thai, Anh ; Stone, James R. ; Coury, Arthur J. ; Weissleder, Ralph ; Langer, Robert ; Anderson, Daniel G. / Painting blood vessels and atherosclerotic plaques with an adhesive drug depot. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 52. pp. 21444-21449.
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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.",
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Kastrup, CJ, Nahrendorf, M, Figueiredo, JL, Lee, H, Kambhampati, S, Lee, T, Cho, S-W, 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, DG 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, vol. 109, no. 52, pp. 21444-21449. https://doi.org/10.1073/pnas.1217972110

Painting blood vessels and atherosclerotic plaques with an adhesive drug depot. / Kastrup, Christian J.; Nahrendorf, Matthias; Figueiredo, Jose Luiz; Lee, Haeshin; Kambhampati, Swetha; Lee, Timothy; Cho, Seung-Woo; Gorbatov, Rostic; Iwamoto, Yoshiko; Dang, Tram T.; Dutta, Partha; Yeon, Ju Hun; Cheng, Hao; Pritchard, Christopher D.; Vegas, Arturo J.; Siegel, Cory D.; MacDougall, Samantha; Okonkwo, Michael; Thai, Anh; Stone, James R.; Coury, Arthur J.; Weissleder, Ralph; Langer, Robert; Anderson, Daniel G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 52, 26.12.2012, p. 21444-21449.

Research output: Contribution to journalArticle

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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.

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