Influence of size, dosage, and surface structure on clearance and tissue distribution of intravenous microspheres

Intravenously injected polystyrene microspheres with functional amino groups (AP-MSs, 0.2, 1.0, and 4.0 mu m in diameter) were cleared from the blood very rapidly. The calculated half-lives for 0.2-, 1.0-, and 4.0-mu m AP-MSs were about 55, 60, and 50 s; no significant differences were found with 10(6), 10(7), and 10(8) microspheres/rat. Loading experiments showed that the liver, spleen, lung, kidney, and heart had a very high capacity to take up AP-MSs. The AP-MSs were distributed mainly to the Liver, lung, and spleen, whereas other organs contained less than 1% of injected AP-MSs. In terms of numbers of AP-MSs per gram of tissue, the highest contents were found in spleen, liver, and lung for 0.2-, 1.0-, and 4.0-mu m AP-MSs, respectively. There was indication of redistribution of particles from one organ to another during the first 6 h after injection. Chondroitin sulfate A (Chon) and hyaluronic acid (Hya) adsorbed or covalently linked to AP-MSs increased uptake in the liver, with Chon AP-MSs (adsorbed or linked) showing the best effect: about 25% increase compared with unadsorbed 1-mu m AP-MSs. Experiments with separated cells in vitro demonstrated that 1 mu m AP-MSs, intravenously injected, associated only with Kupffer cells. When the microspheres were adsorbed with Chon, there was also association with liver endothelial cells. This finding indicates that conjugation of microspheres with ligands for endothelial receptors may be a useful method for directing microspheres to specific organs, even if the receptors are not by themselves phagocytic.