Gustafson Tiffany P, Dergunov Sergey A, Akers Walter J, Cao Qian, Magalotti Selena, Achilefu Samuel, Pinkhassik Eugene, Berezin Mikhail Y
Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110.
RSC Adv. 2013 Jan 24;3(16):5547-5555. doi: 10.1039/C3RA22693J.
Rapid-release drug delivery systems present a new paradigm in emergency care treatments. Such systems combine a long shelf life with the ability to provide a significant dose of the drug to the bloodstream in the shortest period of time. Until now, development of delivery formulations has concentrated on slow release systems to ensure a steady concentration of the drug. To address the need for quick release system, we created hollow polyacrylate nanocapsules with nanometer-thin porous walls. Burst release occurs upon interaction with blood components that leads to escape of the cargo. The likely mechanism of release involves a conformational change of the polymer shell caused by binding albumin. To demonstrate this concept, a near-infrared fluorescent dye indocyanine green (ICG) was incorporated inside the nanocapsules. ICG-loaded nanocapsules demonstrated remarkable shelf life in aqueous buffers with no release of ICG for twelve months. Rapid release of the dye was demonstrated first in vitro using albumin solution and serum. SEM and light scattering analysis demonstrated the retention of the nanocapsule architecture after the release of the dye upon contact with albumin. In vivo studies using fluorescence lifetime imaging confirmed quick discharge of ICG from the nanocapsules following intravenous injection.
速释药物递送系统为急诊治疗带来了新的范例。这类系统兼具较长的保质期以及在最短时间内向血流中提供大剂量药物的能力。到目前为止,递送制剂的研发主要集中在缓释系统,以确保药物浓度稳定。为满足对快速释放系统的需求,我们制备了具有纳米级薄壁的中空聚丙烯酸酯纳米胶囊。与血液成分相互作用时会发生突发释放,导致所载药物逸出。可能的释放机制涉及由结合白蛋白引起的聚合物壳构象变化。为证明这一概念,将近红外荧光染料吲哚菁绿(ICG)包封在纳米胶囊内部。负载ICG的纳米胶囊在水性缓冲液中表现出显著的保质期,十二个月内ICG无释放。首先在体外使用白蛋白溶液和血清证明了染料的快速释放。扫描电子显微镜(SEM)和光散射分析表明,与白蛋白接触后染料释放后纳米胶囊结构得以保留。使用荧光寿命成像的体内研究证实,静脉注射后ICG能从纳米胶囊中快速排出。