Drexel University College of Medicine, Philadelphia PA, USA.
Curr Drug Deliv. 2010 Oct;7(4):263-73. doi: 10.2174/156720110793360621.
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 re-dosing 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 emulsification-solvent 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.
长期预防支架植入后冠状动脉内腔中平滑肌细胞的迁移和增殖仍然是医学上的一个挑战。血管支架已涂有抗增殖药物，如紫杉醇和雷帕霉素，以提高支架的疗效。在冠状动脉支架上保持足够的药物浓度是一个障碍，而磁性纳米颗粒（MNP）药物输送有可能克服这一障碍。已经提出了可生物降解的超顺磁纳米颗粒，由高梯度磁场引导，作为再向抗增殖药物加载支架输送的运输工具。本研究确定了几种候选 MNP 制剂的特性，包括其粒径、表面电荷、磁铁矿和药物负载效率、药物释放曲线以及它们对相关血管细胞的抗增殖作用。使用乳化-溶剂蒸发方法，从聚乳酸和聚（乳酸-共-乙醇酸）聚合物中制备了含有近 30%（w/w）磁铁矿和 12%（w/w）紫杉醇的 MNPs。药物释放模式与用不同 MNP 剂量处理的培养的主动脉平滑肌细胞和牛主动脉内皮细胞的细胞生长抑制密切相关。细胞活力测定显示，紫杉醇负载制剂的 MNP 剂量依赖性细胞生长抑制在 8 天的时间范围内，导致培养的血管平滑肌细胞和内皮细胞的细胞生长分别接近 80%和 100%的抑制，而未负载药物制剂与未处理细胞相比几乎没有变化。结论是，负载相对高水平的磁铁矿和药物的可生物降解聚合物超顺磁纳米颗粒可以作为血管支架靶向应用中的有效载体，并有可能允许重新向耗尽的支架给药，从而延长植入物的生命周期。
