Abstract 4922: Stent-Targeted Delivery of Paclitaxel-Loaded Biodegradable Nanoparticles Mediated by a Uniform Field Induced Magnetization Effect Inhibits Restenosis in the Rat Carotid Model
Introduction Targeted delivery of drug-loaded biodegradable nanoparticles may provide a safe and efficacious alternative or adjunct to drug eluting coatings on stents by enabling repeated drug dosing, individual dose adjustment, and even use of multiple agents. The potential of enhancing the antirestenotic efficacy of nanoparticle formulations by magnetic targeting remains unexplored. We hypothesized that a novel targeting approach based on a uniform field induced magnetization can be used to localize biodegradable magnetizable nanoparticles (MNP) to a stented arterial segment to achieve inhibition of restenosis in the rat carotid stenting model.
Methods Paclitaxel-loaded MNP (260±7 nm) were formulated from polylactide with inclusion of magnetite using a modified emulsification-solvent evaporation method. Rat common carotid arteries were injured by a Fogarty catheter prior to deployment of a 304-grade stainless steel stent. MNP suspensions containing 500 or 50 ng/μl paclitaxel were delivered for 30 sec to the arterial segments with or without a uniform magnetic field (1200 G). The field was maintained for additional 5 min. The extent of restenosis was compared between the groups (n≥6) 14 days post treatment based on the neointima/media ratio and % of cross-sectional narrowing by non-parametric ANOVA.
Results MNP were obtained with a drug entrapment yield of 30%. A MNP dose-dependent inhibition of restenosis was observed under magnetic conditions (p=0.006), while MNP applied without a magnetic field had no significant antirestenotic effect compared to untreated animals. Magnetically targeted nanoparticulate paclitaxel (500 or 50 ng/μl) reduced the neointima/media ratio by 37±13% (p<0.05) and 16±9%, respectively. The cross-sectional narrowing was decreased by 35±19% (p<0.05) and 16±10% in the respective animal groups.
Conclusions Targeted delivery of paclitaxel-impregnated MNP resulted in a significant dose-dependent inhibition of in-stent restenosis in the rat model. The combination of an antirestenotic agent formulated in magnetically responsive biodegradable nanoparticles and a novel targeting approach based on the uniform field induced magnetization represents a promising strategy for preventing in-stent restenosis.