Local delivery of gene vectors from bare-metal stents by use of a biodegradable synthetic complex inhibits in-stent restenosis in rat carotid arteries.

Circulation
Ilia FishbeinR J Levy

Abstract

Local drug delivery from polymer-coated stents has demonstrated efficacy for preventing in-stent restenosis; however, both the inflammatory effects of polymer coatings and concerns about late outcomes of drug-eluting stent use indicate the need to investigate innovative approaches, such as combining localized gene therapy with stent angioplasty. Thus, we investigated the hypothesis that adenoviral vectors (Ad) could be delivered from the bare-metal surfaces of stents with a synthetic complex for reversible vector binding. We synthesized the 3 components of a gene vector binding complex: (1) A polyallylamine bisphosphonate with latent thiol groups (PABT), (2) a polyethyleneimine (PEI) with pyridyldithio groups for amplification of attachment sites [PEI(PDT)], and (3) a bifunctional (amine- and thiol-reactive) cross-linker with a labile ester bond (HL). HL-modified Ad attached to PABT/PEI(PDT)-treated steel surfaces demonstrated both sustained release in vitro over 30 days and localized green fluorescent protein expression in rat arterial smooth muscle cell cultures, which were not sensitive to either inhibition by neutralizing anti-Ad antibodies or inactivation after storage at 37 degrees C. In rat carotid studies, deployment of...Continue Reading

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Dec 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ilia FishbeinRobert J Levy
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Citations

Sep 30, 2010·Biomedical Engineering Online·Luis A BritoMansoor M Amiji
Mar 3, 2010·Nature Reviews. Cardiology·Rainer Wessely
Feb 15, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Michael ChornyRobert J Levy
Feb 12, 2013·Molecular Pharmaceutics·Debbie GohAlexander M Seifalian
May 26, 2009·Expert Opinion on Biological Therapy·Deirdre M O'Connor, Timothy O'Brien
Feb 26, 2016·Biomaterials·Joshua B SleeStanley J Stachelek
Feb 26, 2016·Nanomedicine·Mahdi KarimiMichael R Hamblin
Apr 17, 2012·Nitric Oxide : Biology and Chemistry·Matthew J AlefBrian S Zuckerbraun
Oct 15, 2009·Journal of Biomedical Materials Research. Part a·Seungjin ShinLonnie D Shea
Apr 26, 2016·Nanomedicine·Mahsa BagheriMohammad Ramezani
Sep 13, 2016·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Ilia FishbeinRobert J Levy
Feb 1, 2010·Viruses·Paul D WilliamsPaul A Kingston
Jan 15, 2020·Acta Biomaterialia·Vaishali V InamdarStanley J Stachelek

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