| In vivo PEG modification of vascular surfaces for targeted delivery. | |
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MedLine Citation:
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PMID: 22169667 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: Thrombosis and restenosis remain problematic for many intravascular procedures. Previously, it has been demonstrated that modifying an injured vascular surface with a protein-reactive polymer could block undesirable platelet deposition. As an added benefit, it would be advantageous if one could target therapeutics to the injured site. This study investigates a site-specific delivery system to target microspheres to vascular surfaces modified with a reactive polyethylene glycol tagged with biotin. METHODS: Rabbit femoral arteries were injured with a 2F embolectomy catheter. Modification of the vascular surface was achieved using a channeled balloon catheter or small-diameter tube. Microspheres were injected intravenously through catheterization of the ear vein. Polymer modification on the injured surface and delivery of microspheres was quantified using epifluorescence microscopy at 0, 24, 48, and 72 hours. RESULTS: Polymer modification of the vascular surface could be achieved using a channeled drug delivery catheter or small-diameter tube with similar results. Maximum polymer coverage occurred at 0 hours and decreased to 85% maximal at 24 hours, 72% at 48 hours, and 67% at 72 hours. The initial number of microspheres per mm(2) binding to modified, injured arteries was 304 versus 141 for the unmodified, damaged control (P < .01). At subsequent times, the number of adherent microspheres to modified, injured arteries decreased by 50%, 70%, and 84% at 24, 48, and 72 hours, respectively; while nonspecific binding to unmodified, injured arteries quickly decreased by 93%. Initial microsphere binding to modified, healthy arteries was 153 microspheres/mm(2) as opposed to 26 microspheres/mm(2) for the unmodified, healthy controls (P < .01). CONCLUSIONS: Chemical modification of injured vessels following intravascular procedures can be readily accomplished in vivo to create a substrate for targeted delivery systems. As a proof of concept, targeted microspheres preferentially adhered to polymer-modified surfaces as opposed to injured, unmodified, or healthy vascular surfaces. |
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Authors:
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Timothy E Deglau; Timothy M Maul; Flordeliza S Villanueva; William R Wagner |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-9 |
Journal Detail:
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Title: Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter Volume: - ISSN: 1097-6809 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8407742 Medline TA: J Vasc Surg Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved. |
Affiliation:
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Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, Pittsburgh, Pa. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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