Published online before print August 19, 2002, doi: 10.1161/01.CIR.0000032141.31476.15
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(Circulation. 2002;106:1195.)
© 2002 American Heart Association, Inc.
Brief Rapid Communications |
Sustained Reduction of In-Stent Neointimal Growth With the Use of a Novel Systemic Nanoparticle Paclitaxel
From the Department of Cardiovascular Pathology (F.D.K., M.J., C.K., A.F., P.S.W., E.A., R.V.), Armed Forces Institute of Pathology, Washington, DC; and American Bioscience Inc (N.D., P.S.-S.), Santa Monica, Calif.
Correspondence to Renu Virmani, MD, Chairperson, Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Building 54, Room 2005, 6825 16th St, Washington, DC 20306. E-mail virmani{at}afip.osd.mil
Background— Paclitaxel (PXL)-eluting stents in animals cause incomplete healing and, in some instances, a lack of sustained suppression of neointimal growth. The present study tested the efficacy of a novel systemic delivery nanoparticle PXL for reducing in-stent restenosis.
Methods and Results— A saline-reconstituted formulation of PXL stabilized by albumin nanoparticles (nPXL) was tested in 38 New Zealand White rabbits receiving bilateral iliac artery stents. Doses of nPXL (1.0 to 5.0 mg/kg) were administered as a 10-minute intra-arterial infusion; control animals received vehicle (0.9% normal saline). In a follow-up chronic experiment, nPXL 5.0 mg/kg was given at stenting with or without an intravenous 3.5-mg/kg repeat nPXL dose at 28 days; these studies were terminated at 3 months. At 28 days, mean neointimal thickness was reduced (P
0.02) by doses of nPXL 
2.5 mg/kg with evidence of delayed healing. The efficacy of a single dose of nPXL 5.0 mg/kg, however, was lost by 90 days. In contrast, a second repeat dose of nPXL 3.5 mg/kg given 28 days after stenting resulted in sustained suppression of neointimal thickness at 90 days (P0.009 versus single dose nPXL 5.0 mg/kg and controls) with nearly complete neointimal healing.
Conclusions— Although systemic nPXL reduces neointimal growth at 28 days, a single repeat dose was required for sustained neointimal suppression. Thus, this novel systemic formulation of PXL may allow adjustment of dose at the stent treatment site and prove to be a useful adjunct for the clinical prevention of in-stent restenosis.
Key Words: arteries • drugs • muscle, smooth • restenosis • stents
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