Magnetically Responsive Paclitaxel-Loaded Biodegradable Nanoparticles for Treatment of Vascular Disease: Preparation, Characterization and In Vitro Evaluation of Anti-Proliferative Potential

Brandon      Johnson; Brent      Toland; Rishi      Chokshi; Vadym      Mochalin; Sirma      Koutzaki; Boris      Polyak

Abstract

Long term prevention of smooth muscle cell migration and proliferation inside the lumen of coronary arteries after stent implantation remains a challenge in medicine. Vascular stents have been coated with anti-proliferative drugs such as paclitaxel and rapamycin to improve the stents efficacy. Maintaining adequate drug concentration on coronary stents presents an obstacle which magnetic nanoparticle (MNP) drug delivery could potentially overcome. Biodegradable, super-paramagnetic nanoparticles guided by high gradient magnetic fields have been proposed as transport vehicles for redosing stents with anti-proliferative drugs. The current study determined the characteristics of a number of candidate MNP formulations in terms of their size, surface charge, efficiency of magnetite and drug loadings, drug release profiles as well as their anti-proliferative effect on the relevant vascular cells. MNPs containing near 30% (w/w) magnetite and 12% (w/w) paclitaxel were formulated from polylactide and poly(lactide-co-glycolide) polymers using an emulsificationsolvent evaporation methodology. Drug release patterns correlated well with cell growth inhibition in cultured aortic smooth muscle cells and bovine aortic endothelial cells treated with varying MNP doses. Cell viability assays revealed MNP dose-dependent cell growth inhibition over an 8-day time span for paclitaxel-loaded formulations resulting in near 80% and 100% of cell growth arrest in cultured vascular smooth muscle cells and endothelial cells respectively, while unloaded with drug formulations showed negligible variation from the non treated cells. It is concluded, that biodegradable polymeric superparamagnetic nanoparticles loaded with a relatively high level of magnetite and drug could serve as efficient carriers in vascular stent targeting applications and potentially allow re-dosing the depleted stents, thereby prolonging the lifecycle of the implant.

Keywords: Magnetic nanoparticles, paclitaxel, magnetic drug delivery, drug release, biodegradable polymers, vascular disease