Medical Policlinic, University Hospital Munich, Ziemssenstrasse 1, Munich, Germany.
Pharm Res. 2012 May;29(5):1295-307. doi: 10.1007/s11095-011-0643-y. Epub 2011 Dec 22.
Coating coronary stents with antirestenotic drugs revolutionized interventional cardiology. We developed a system for post-hoc drug delivery to uncoated stents.
We coupled rapamycin or a chemically similar fluorescent dye to superparamagnetic nanoparticles. The antiproliferative activity of rapamycin coupled to nanoparticles was confirmed in vitro in primary porcine vascular cells. The particles were then incorporated into lipid based microbubbles. Commercially available stents were made magnetizable by nickel plating and used to induce strong field gradients in order to capture magnetic microbubbles from flowing liquids when placed in an external magnetic field.
Nanoparticle bound Rapamycin dose dependently inhibited cell proliferation in vitro. Magnetic microcbubbles carrying coated nanoparticles were caught by magnets placed external to a flow-through tube. Plating commercial stents with nickel resulted in increased deposition at stent struts and allowed for widely increased distance of external magnets. Deposition depended on circulation time and velocity and distance of magnets. Deposited microbubbles were destroyed by ultrasound and delivered their cargo to targeted sites.
Drugs can be incorporated into nanoparticle loaded microbubbles and thus be delivered to magnetizable stents from circulating fluids by applying external magnetic fields. This technology could allow for post-hoc drug coating of already implanted vascular stents.
用抗再狭窄药物对冠状动脉支架进行涂层使介入心脏病学发生了革命性的变化。我们开发了一种对未涂层支架进行药物后输送的系统。
我们将雷帕霉素或化学性质相似的荧光染料与超顺磁性纳米颗粒偶联。在原代猪血管细胞中体外证实了与纳米颗粒偶联的雷帕霉素的抗增殖活性。然后将这些颗粒纳入脂质基微泡中。通过镀镍使市售支架具有可磁化性，并在外磁场中使用这些支架来诱导强磁场梯度，以便在流动液体中捕获磁性微泡。
与纳米颗粒结合的雷帕霉素剂量依赖性地抑制了体外细胞增殖。携带涂覆有纳米颗粒的磁性微泡被放置在流动管外部的磁铁捕获。用镍对商用支架进行镀镍处理会导致支架支柱上的沉积增加，并允许外部磁铁的距离大大增加。沉积取决于循环时间、速度以及磁铁的距离。沉积的微泡被超声破坏，并将其有效载荷输送到靶向部位。
药物可以被包裹在载有纳米颗粒的微泡中，然后通过施加外部磁场，从循环液中将其递送到可磁化的支架上。这项技术可以对已经植入的血管支架进行药物后涂层处理。
