Abstract 13845: Intramural Delivery of Pitavastatin Using a Novel Composite Drug Delivery System (Nanoparticle and Pulse Wave Infusion Catheter) Attenuates Neointima Formation after Balloon Injury in Porcine Coronary Arteries
Background: We recently reported the local intramural delivery and retention of nanoparticle (NP) for 4 weeks into wire-induced injured murine femoral arteries with a 5-minute incubation of NP by temporarily ligating the artery using snares. Because the ligation approach has a limitation to the clinical applicability, we developed a new catheter-based DDS called pulse wave infusion catheter that is equipped with pulse wave infusion device (Fig. A). The purpose of this study was to test the hypothesis that local delivery of pitavastatin using a composite of NP- and catheter-mediated DDS attenuates neointima formation after balloon injury in porcine coronary arteries.
Methods and Results: Among 6 marketed statins, pitavastatin (Pitava) was found to be most potent effects on vascular smooth muscle cells (VSMCs) proliferation in vitro. Porcine coronary arteries were injured by overstretch with balloon catheter (balloon to artery ratio=1.2) and thereafter NP containing 1.3 mg FITC or 4.0 mg pitavastatin was injected into the injured sites with the pulse wave infusion catheter. At week 4, FITC fluorescence signals were found only in the injured coronary arterial sites treated with FITC-NP, especially in the medial layer that mainly consists of VSMCs (Fig. B). Importantly, treatment with Pitava-NP attenuated neointima formation (modified restenosis injury index: 3.64±0.27 vs 4.49±0.23, p<0.05, n=11 each; Fig. C).
Conclusions: Intramural delivery of pitavastatin with this composite DDS inhibited neointima formation after balloon injury in porcine coronary arteries. This novel composite DDS can diminish adverse effects related to drugs and be developed as a new therapeutic technology of nanomedicine for anti-restenotic drug treatment that could be undergone during clinical catheter-based interventions without the use of drug-eluting stents.
- © 2012 by American Heart Association, Inc.