Abstract 2037: Sustained Intracellular Delivery of Nanoparticles in Porcine Coronary Arteries from a Bioabsorbable Polymeric Nanoparticle-Eluting Stent
Background Currently marketed first-generation drug-eluting stent still has several limitations that include delayed endothelial regeneration, healing (late inflammation, proliferation, and fibrin deposition) and in-stent thrombosis. These adverse effects may be caused by anti-proliferative effects on endothelial cells due to the drug, or non-bioabsorbable polymers. In addition, current polymeric coating methods use the dip-coating (i.e. passive coating) of polymer-drug matrix, leading to inadequate dose of the drug on stent and low delivery rate of the drug from the stent. To overcome these limitations, we developed a novel actively-controlled coating technology using bioabsorbable polymeric nanoparticles (NP). Therefore, the aim of this study is to produce a novel bioabsorbable polymeric NP-eluting stent and to evaluate intracellular delivery of NP in porcine coronary arteries in vivo.
Methods and results We prepared fluorescence (FITC)-encapsulated poly-lactic-glycolic acid copolymer NP (mean diameter: 200 nm), which surface was negatively charged, by the emulsion solvent diffusion method. We succeeded to produce the homogenous multi-layer coating stent by electrifying direct current to stent steeped in NP solution. To verify intracellular delivery of NP, piece of NP-coated stent strut was placed in the dish of vascular smooth muscle cells in culture. After 2 hours, NP were uptaken by almost all cells (> 99%), and found in cytoplasmic and peri-nuclear areas. We then implanted the NP-eluting or bare metal control stents in porcine coronary arteries. Interestingly, after 14 and 28 days when the neointima was already formed, intense fluorescence was observed not only in most of cells around the stent strut, but also in many cells in the neointima and adventitia. In a 28-day observation period, no evidence of abnormal inflammation in response to NP-eluting stents was noted.
Conclusion We have developed a novel active-coating technology to produce bioabsorbable polymeric NP-eluting stent, and demonstrated successful intracellular delivery in porcine coronary arteries in vivo. The present technique demonstrates the potential usefulness of polymeric NP-eluting stents, resulting in sustained intracellular drug/gene delivery system.