Sustained reduction of in-stent neointimal growth with the use of a novel systemic nanoparticle paclitaxel.
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.


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< or =0.02) by doses of nPXL > or =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 (P< or =0.009 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.
Kolodgie
Frank D
FD
Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306, USA.
John
Michael
M
Khurana
Charanjit
C
Farb
Andrew
A
Wilson
Patricia S
PS
Acampado
Eduardo
E
Desai
Neil
N
Soon-Shiong
Patrick
P
Virmani
Renu
R
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D001158:Arteries / Q000473:pathology / Q000648:ultrastructure; D006083:Graft Occlusion, Vascular / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007700:Kinetics; D007958:Leukocyte Count; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010316:Particle Size; D011817:Rabbits; D015607:Stents / Q000009:adverse effects*
D020533:Angiogenesis Inhibitors; D017239:Paclitaxel