Department of Chemical and Biochemical Engineering, University of Western Ontario, 1151 Richmond Street, London, Ontario, Canada.
AAPS PharmSciTech. 2013 Sep;14(3):977-93. doi: 10.1208/s12249-013-9980-y. Epub 2013 Jun 14.
The present work describes the in vitro aerosol deposition and enhanced deaggregation behavior of superparamagnetic iron oxide nanoaggregates (SPIONs). SPIONs were surface-coated with amine functionalized polyrotaxane and were proposed as a carrier for inhalation dry powders. Polyrotaxane is primarily composed of beta cyclodextrin rings which are spontaneously threaded on the block copolymer, poly(propylene glycol) bis(2-aminopropylether). Variable concentrations of surface coating polymers showed controlled manipulation of the crystal size and morphology. Magnetic nanoaggregates fabricated with low concentration of polyrotaxane showed cubic crystal morphology. However, these nanoaggregates exhibited rhombic dodecahedron crystal structure upon increasing the coating polymer concentration. In comparison to the spherical uncoated magnetic nanoparticles, cubic phase magnetic nanoaggregates demonstrated an enhanced in vitro aerosol deposition using magnetic field alignment. This enhancement can be accomplished at low inhalation flow rates (15 and 30 L/min). However, transformation to the cubic crystal structure was observed to be associated with a reduction in the powder geometric standard deviation. Using a mathematical modeling approach, we noted significant enhancement in the deaggregation behavior of inhalation dry powders; that can be achieved with small amounts of magnetic nanoaggregates. Aggregates of cubic nanoparticles showed promise for targeted pulmonary deposition of anticancer drugs.
本工作描述了超顺磁性氧化铁纳米聚集体(SPIONs)的体外气溶胶沉积和增强解团聚行为。SPIONs 表面涂覆有胺官能化聚轮烷,被提议作为吸入干粉的载体。聚轮烷主要由 β 环糊精环组成,这些环可以自发地穿在嵌段共聚物聚(丙二醇)双(2-氨基丙醚)上。表面涂层聚合物的浓度变化可以控制晶体尺寸和形态。用低浓度聚轮烷制备的磁性纳米聚集体呈现立方晶体形态。然而,当增加涂层聚合物浓度时,这些纳米聚集体表现出菱面体十二面体的晶体结构。与球形未涂层的磁性纳米颗粒相比,立方相磁性纳米聚集体在磁场定向作用下表现出增强的体外气溶胶沉积。这种增强可以在低吸入流速(15 和 30 L/min)下实现。然而,观察到向立方晶体结构的转变与粉末几何标准偏差的降低有关。使用数学建模方法,我们注意到吸入干粉的解团聚行为有显著增强;这可以通过少量的磁性纳米聚集体来实现。立方纳米颗粒的聚集体有望实现抗癌药物的靶向肺沉积。