Abstract 5899: Nanoparticle-Mediated Delivery of Pioglitazone Effectively Attenuates Neointimal Formation After Wire Injury in Mice
Background: Currently marketed drug-eluting stents (DES) reduce restenosis, however, they have raised serious safety concerns including late stent thrombosis. Recently, systemic administration of a peroxisome proliferator activated receptor-γ(PPARγ) agonist pioglitazone reduces the incidence of ischemic cardiovascular events including restenosis. We therefore considered that selective delivery of pioglitazone may optimize its beneficial effects and alleviate its adverse effects. In this study, we tested the hypothesis that PLGA nanoparticle (NP)-mediated delivery of pioglitazone into the arterial wall effectively inhibits neointimal formation after wire injury in murine model.
Methods and Results: We performed wire injury in temporary ligated mouse femoral arteries and injected FITC- loaded NP (FITC-NP, 0.15 mg), pioglitazone (0.012 mg), or pioglitazone-loaded NP (Pio-NP) containing 0.012 mg of pioglita-zone for 5 minutes followed by recanalization (Figure A⇓). In FITC-NP treated group, significant FITC fluorescence was noted mainly in vascular smooth muscle cells in the media for up to 21 days post-injury (Figure B⇓), indicating efficient and stable delivery of NP into the injured artery. We analyzed neointimal formation as intima to media ratio (I/M ratio) 28 days after injury. Treatment with Pio-NP, but not with FITC-NP or pioglitazone only, effectively attenuated neointimal formation (Figure C⇓) and suppressed MCP-1 expression and macrophage infiltration in the injured arterial wall.
Conclusion: NP-mediated delivery of pioglitazone into injured artery may be a novel therapeutic approach to inhibit restenosis after intraluminal angioplasty.