Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
J Control Release. 2010 Apr 2;143(1):31-7. doi: 10.1016/j.jconrel.2009.12.019. Epub 2010 Jan 5.
The relationship between microparticle (MP) size and lung targeting efficiency, intra-lung distribution and retention time was systematically studied after intravenous administration of rigid fluorescent polystyrene MPs of various sizes (2, 3, 6 and 10 microm) to Sprague Dawley rats. Total fluorescence was assessed and it was found that 2 microm and 3 microm MPs readily passed through the lung to the liver and spleen while 10 microm MPs were completely entrapped in the lung for the one-week duration of the study. Approximately 84% of 6 microm MPs that were initially entrapped in the lung were cleared over the next 2 days and 15% were cleared over the remaining 5 days. A Caliper IVIS 100 small animal imaging system confirmed that 3 microm MPs were not retained in the lung but that 6 microm and 10 microm MPs were widely distributed throughout the lung. Moreover, histologic examination showed MP entrapment in capillaries but not arterioles. These studies suggest that for rigid MPs the optimal size range required to achieve transient but highly efficiently targeting to pulmonary capillaries after IV injection is >6 microm but <10 microm in rats and that systemic administration of optimally sized MPs may be an efficient alternative to currently used inhalation-based delivery to the lung.
静脉注射不同大小（2、3、6 和 10 微米）刚性荧光聚苯乙烯 MPs 后，系统研究了 MPs 粒径与肺部靶向效率、肺部内部分布和滞留时间之间的关系。评估了总荧光强度，发现 2 微米和 3 微米 MPs 很容易穿过肺部到达肝脏和脾脏，而 10 微米 MPs 在研究的一周内完全被肺部截留。最初被肺部截留的 6 微米 MPs 中有约 84%在接下来的 2 天内被清除，15%在剩余的 5 天内被清除。 Caliper IVIS 100 小动物成像系统证实，3 微米 MPs 不会在肺部滞留，但 6 微米和 10 微米 MPs 在肺部广泛分布。此外，组织学检查显示 MPs 被截留于毛细血管中，而不是小动脉中。这些研究表明，对于刚性 MPs，在静脉注射后实现对肺部毛细血管的短暂但高效靶向作用所需的最佳粒径范围为>6 微米但<10 微米，在大鼠中，大小优化的 MPs 的全身给药可能是目前基于吸入式肺部给药的有效替代方法。
