Following recent successes with
percutaneous coronary intervention (PCI) for treating
coronary artery disease (CAD), many challenges remain. In particular, mechanical injury from the procedure results in extensive endothelial denudation, exposing the underlying
collagen IV-rich basal lamina, which promotes both intravascular
thrombosis and smooth muscle proliferation. Previously, we reported the engineering of
collagen IV-targeting nanoparticles (NPs) and demonstrated their preferential localization to sites of arterial injury. Here, we develop a systemically administered, targeted NP system to deliver an antiproliferative agent to injured vasculature. Approximately 60-nm
lipid-polymeric NPs were surface functionalized with
collagen IV-targeting
peptides and loaded with
paclitaxel. In safety studies, the targeted NPs showed no signs of toxicity and a ≥3.5-fold improved maximum tolerated dose versus
paclitaxel. In efficacy studies using a rat carotid injury model,
paclitaxel (0.3 mg/kg or 1 mg/kg) was i.v. administered postprocedure on days 0 and 5. The targeted NP group resulted in lower
neointima-to-media (N/M) scores at 2 wk versus control groups of saline,
paclitaxel, or nontargeted NPs. Compared with
sham-injury groups, an ∼50% reduction in arterial
stenosis was observed with targeted NP treatment. The combination of improved tolerability, sustained release, and vascular targeting could potentially provide a safe and efficacious option in the management of CAD.