Abstract 2479: Site Specific Targeting of Nanoparticle Prednisolone Prevents in-Stent Restenosis In a Rabbit Model of Established Atheroma
Background– TRM-484 (a prednisolone delivered nanoparticle) has been shown to reduce smooth muscle cell (SMC) proliferation and macrophage migration in vitro. In a stent injury model, we tested the ability of TRM-484 to be delivered to injured sites and its capability to reduce neointimal growth.
Methods– Atherosclerotic New Zealand White Rabbits were implanted bare metal stents and randomized to receive intravenous TRM-484 at doses of 1mg/kg (high dose) or 0.32mg/kg (low dose) from the day of stenting three-times a week. Control animals received either empty liposomes (placebo) or saline infusion. Stented arterial segments were harvested at 42 days and processed for histomorphometry and immunohistochemistry. Selected animals received rhodamine-labelled TRM-484 and arterial segments were harvested at 24 hours and 7 days after stenting. Confocal microscopy was used to characterize arterial drug distribution (red channel) in sections stained for SMC’s (HHF, panel A) and macrophages (RAM11, panel B) (green channel).
Results– TRM-484 was exclusively observed at sites of stent strut-induced injury, with absence of drug in contralateral non-stented arteries. High dose TRM-484 resulted in significant reduction of percent stenosis compared to saline and placebo treated rabbits (22.8±4.5 vs. 31.9±9.6 and 30.9±9.4 %, p<0.02).
Conclusion– TRM-484 at doses of 1mg/kg resulted in sustained suppression of in-stent neointimal growth in atherosclerotic rabbits. Site-specific targeting by steroids in injured atherosclerotic areas might be a valuable and cost-effective approach for prevention of in-stent restenosis.