title: Painting blood vessels and atherosclerotic plaques with an adhesive drug depot.
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.
authors.affiliation: Department of Chemical Engineering and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Kastrup
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Jose Luiz
authors.initials: JL
authors.lastname: Figueiredo
authors.forename: Haeshin
authors.initials: H
authors.lastname: Lee
authors.forename: Swetha
authors.initials: S
authors.lastname: Kambhampati Thiruvengadam
authors.forename: Timothy
authors.initials: T
authors.lastname: Lee
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Rostic
authors.initials: R
authors.lastname: Gorbatov
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Tram T
authors.initials: TT
authors.lastname: Dang
authors.forename: Partha
authors.initials: P
authors.lastname: Dutta
authors.forename: Ju Hun
authors.initials: JH
authors.lastname: Yeon
authors.forename: Hao
authors.initials: H
authors.lastname: Cheng
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pritchard
authors.forename: Arturo J
authors.initials: AJ
authors.lastname: Vegas
authors.forename: Cory D
authors.initials: CD
authors.lastname: Siegel
authors.forename: Samantha
authors.initials: S
authors.lastname: MacDougall
authors.forename: Michael
authors.initials: M
authors.lastname: Okonkwo
authors.forename: Anh
authors.initials: A
authors.lastname: Thai
authors.forename: James R
authors.initials: JR
authors.lastname: Stone
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Coury
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D000268:Adhesiveness / Q000187:drug effects; D000269:Adhesives / Q000737:chemistry*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D001158:Arteries / Q000187:drug effects / Q000473:pathology; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology*; D002396:Catechols / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000473:pathology*; D012995:Solubility; D013314:Stress, Mechanical; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D000269:Adhesives; D001057:Apolipoproteins E; D002396:Catechols; D005782:Gels; D003907:Dexamethasone; C034221:catechol