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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1879.)
© 2008 American Heart Association, Inc.

Editorials

From Systemic Shotgun to Site-Specific Nanoparticle-Targeted Delivery

A New Paradigm for Drug Delivery

Ian J. Sarembock

From the Ohio Heart & Vascular Center, The Lindner Clinical Research Center and The Heart & Vascular Center, The Christ Hospital, Cincinnati.

Correspondence to Ian J. Sarembock, MB, ChB, MD, Ohio Heart & Vascular Center & The Lindner Clinical Research Center, 2123 Auburn Avenue, Suite 136, Cincinnati, Ohio 45219. E-mail Sarembock@ohioheart.org

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Since the introduction of percutaneous techniques for the relief of symptomatic obstructive atherosclerotic coronary artery disease in the late 1970s, the major Achilles heel was restenosis. After nearly 3 decades of study, the cellular and molecular biology of this complex response to injury is now far better understood and includes the role of thrombosis, cellular proliferation, inflammation, matrix production, and elastic recoil.^1,2 Some 15 years ago there was enthusiastic interest in the concept of "site specific" or "direct delivery" of antiproliferative or anticoagulant therapies.^3–6 Edelman et al reported on the inhibition of SMC proliferation after vascular injury by surgical placement of heparin-impregnated polymer matrix in the periadventitial tissue of rat carotid arteries.³ At that time a catheter-based porous balloon catheter became available for "site specific" delivery⁷ but failed to be effective in limiting restenosis in an atherosclerotic rabbit femoral artery injury model.⁴ Although labeled heparin could be demonstrated to be present in the injured vessel wall, retention time of the drug and potential additional injury created by a jet effect of the porous balloon catheter were cited as potential explanations for the lack of efficacy. Subsequently, the concept of local delivery remained dormant and a multitude of clinical trials using systemically administered pharmacological agents to reduce or prevent restenosis demonstrated no benefit.⁸

See accompanying article on page 1960

In the late 1980s and early 1990s, coronary stents, providing the necessary scaffolding to prevent elastic recoil become the new standard for the percutaneous treatment of obstructive coronary disease.⁹ Nevertheless, in-stent restenosis . . . [Full Text of this Article]

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Site-Specific Targeting of Nanoparticle Prednisolone Reduces In-Stent Restenosis in a Rabbit Model of Established Atheroma

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Arterioscler Thromb Vasc Biol 2008 28: 1960-1966. [Abstract] [Full Text] [PDF]