Abstract 3443: Nanoparticle-Mediated Intracellular Delivery of Imatinib, a PDGF Receptor Tyrosine Kinase Inhibitor, in Porcine Coronary Arteries from Nanoparticle-Eluting Stent Attenuates Neointimal Formation
Background: Increased risk of late in-stent thrombosis resulting in acute myocardial infarction after the use of the first-generation drug-eluting stents (DES) has become a big problem. This serious adverse effect may result from the drug-induced impairment of endothelial regeneration and from the use of non-biocompatible polymers. The DES system with less adverse effects, therefore, is needed. To this end, we developed a stent coating technology with bioabsorbable polymeric nanoparticles (NP). Platelet-derived growth factor (PDGF), expressed by vascular smooth muscle cells (SMCs), plays a central role in the pathogenesis of restenosis after coronary stenting. Imatinib is an inhibitor of PDGF receptor tyrosine kinase and is approved for clinical use. We hypothesized that imatinib-incorporated NP-eluting stent attenuates neointimal formation with no adverse effects in vivo.
Methods and results: We prepared imatinib- or fluorescence (FITC)-incorporated PLGA NP with cationized surface by chitosan, and developed NP-eluting stent by electrodeposition. The NP eluted from the stent was uptaken with high efficiency (> 99 %) by cultured SMCs. In a pig coronary artery stent model, FITC was observed in coronary arterial cells after 4 weeks in FITC-NP-eluting stent group. NP-mediated delivery of imatinib (21 ± 8 μg/stent) markedly attenuated neointimal formation 28 days after stenting compared with BMS and FITC-NP-eluting stents (Figure⇓).
Conclusion: NP-mediated intracellular delivery of imatinib from NP-eluting stent effectively attenuates neointimal formation in porcine coronary arteries in vivo. This system can be a future direction for NP-based medical device.