Threshold size for optimal passive pulmonary targeting and retention of rigid microparticles in rats

Abstract

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 10μm) to Sprague-Dawley rats. Total fluorescence was assessed and it was found that 2μm and 3μm MPs readily passed through the lung to the liver and spleen while 10μm MPs were completely entrapped in the lung for the one-week duration of the study. Approximately 84% of 6μm 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 3μm MPs were not retained in the lung but that 6μm and 10μm 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 >6μm but <10μm in rats and that systemic administration of optimally sized MPs may be an efficient alternative to currently used inhalation-based delivery to the lung. KeywordsPassive pulmonary targeting; Rigid non-biodegradable microparticle; In vivo imaging

Engineered nanomaterial uptake and tissue distribution: from cell to organism

“…In vivo studies in the rat using polystyrene particles demonstrated passive accumulation in the lung for particles with a size exceeding a threshold of 10 µm. 121 Thus, findings of lung targeting of ENMs may be indicative of "accidental" trapping of agglomerates. 122 As mentioned above, phagocytosis of ENMs is an additional …”

Higher lung accumulation of intravenously injected organic nanotubes

“…When the average volume of the tumors reached 100-150 mm 3 , free CPT-11 in saline, CPT-11/ONT in saline, and Gd-ONT in saline containing 0.1% Tween 80 were intravenously injected via the lateral tail veins. Free CPT-11 at a dose of 4 mg CPT-11/kg, CPT-11/ONT at a dose of 100 mg ONT/kg corresponding to a concentration of 2-3.5 mg CPT-11/kg, and Gd-ONT at a dose of 50 mg ONT/kg corresponding to a concentration of 6.3 mg Gd/kg were applied.…”

“…1 With regard to particle size, smaller nonbiodegradable rigid polystyrene microparticles (MPs) (,4 µm) pass through the lung and become entrapped in the organs of the reticuloendothelial system (RES), such as the liver and spleen 2,3 and larger MPs are accumulated in the lung. 3 For surface properties, it is well established that modification with polyethylene glycol (PEG) chains helps nanosized particles to evade RES uptake and thus remain in the circulation for a longer time. Non-PEGylated, nanosized liposomes consistently tend to accumulate in RES.…”

“…The biodistribution of various sized MPs has been reported. 3 Similar-sized spherical particles to the diameter of ONTs, approximately 100 nm non-PEGylated liposomes and MPs are already known to be accumulated in RES. 4 More than 4 µm-sized MPs accumulated in the lung in rats, 3 and therefore 3 µm-sized MPs may accumulate in lung of mice.…”

“…3 Similar-sized spherical particles to the diameter of ONTs, approximately 100 nm non-PEGylated liposomes and MPs are already known to be accumulated in RES. 4 More than 4 µm-sized MPs accumulated in the lung in rats, 3 and therefore 3 µm-sized MPs may accumulate in lung of mice. Here, we present a preliminary analysis of how the shape of the particles can affect their accumulation in major organs after intravenous injection.…”