Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
Int J Nanomedicine. 2013;8:315-23. doi: 10.2147/IJN.S38462. Epub 2013 Jan 18.
The size and shape of intravenously injected particles can affect their biodistribution and is of importance for the development of particulated drug carrier systems. In this study, organic nanotubes (ONTs) with a carboxyl group at the surface, a length of approximately 2 μm and outer diameter of 70-90 nm, were injected intravenously into tumor-bearing mice. To use ONTs as drug carriers, the biodistribution in selected organs of ONTs postinjection was examined using irinotecan, as an entrapped water-soluble marker inside ONTs, and gadolinium-chelated ONT, as an ONT marker, and compared with that of a 3 μm fluorescently labeled spherical microparticle which was similar size to the length of ONTs. It was found that for irinotecan, its active metabolite and gadolinium-chelated ONTs were highly accumulated in the lung, but to a lower level in the liver and spleen. On the other hand, microparticles deposited less in the lung and more highly in the liver. Moreover, histologic examination showed ONTs distributed more in lung tissues in part, whereas microparticles were present in blood vessels postinjection. These preliminary results support the notion of using negatively charged ONTs as intravascular carriers to maximize accumulation in the lung whilst reducing sequestration by the liver and spleen. This finding suggested that ONTs are potential carriers for lung-targeting drug delivery.
静脉内注射的粒子的大小和形状会影响其生物分布,这对于开发颗粒药物载体系统非常重要。在这项研究中,表面带有羧基的有机纳米管(ONTs)被注入患有肿瘤的小鼠体内。为了将 ONTs 用作药物载体,使用伊立替康(作为 ONTs 内包裹的水溶性标记物)和钆螯合的 ONTs(作为 ONT 标记物)检查了 ONTs 注射后在选定器官中的分布情况,并与 3μm 荧光标记的球形微球进行了比较,后者的尺寸与 ONTs 的长度相似。结果发现,伊立替康的活性代谢物和钆螯合的 ONTs 在肺部高度积累,但在肝脏和脾脏中的积累程度较低。另一方面,微球在肺部的沉积较少,而在肝脏中的沉积较多。此外,组织学检查显示,部分 ONTs 在肺部组织中的分布更多,而微球在注射后存在于血管中。这些初步结果支持使用带负电荷的 ONTs 作为血管内载体的观点,以最大限度地增加肺部的积累,同时减少肝脏和脾脏的隔离。这一发现表明,ONTs 是一种有潜力的肺部靶向药物传递载体。