EFFECT OF SPLENIC CONGESTION ASSOCIATED WITH HEMOLYTIC-ANEMIA ON FILTRATION OF SPLEEN-HOMING MICROSPHERES

1. The surface of large model I-125-labelled polystyrene microspheres (220 nm in diameter) was coated with the polyoxyethylene/polyoxypropyl ene block co-polymer poloxamine-908. The coated microspheres were inje cted intravenously into rats. Up to 40% of the administered dose had a ccumulated in the spleen by a filtration mechanism, as compared with 5 % for uncoated microspheres, at 3 h after administration. The enhanced splenic sequestration of microspheres was accompanied by a decrease i n the liver uptake. In contrast, smaller poloxamine-908-coated microsp heres (60 nm in diameter) effectively avoided uptake by both the liver and the spleen and remained in systemic circulation. 2. The effect of splenic congestion, associated with phenylhydrazine-induced haemolyti c anaemia, on filtration of poloxamine-908-coated microspheres was stu died. The enlarged spleen of the anaemic rats was incapable of efficie ntly filtering large poloxamine-908-coated microspheres when compared with the spleen of normal animals. This was suggested to be the result of extensive 'clogging' of the red pulp by damaged erythrocytes. Howe ver, the splenic filtration of large coated microspheres was still fiv e-fold higher than that of uncoated microspheres of similar size in an aemic animals. 3. The potential use of large sterically stabilized col loids and drug carriers for selective spleen scanning and splenic drug delivery in pathological conditions, where anaemia prevails, is discu ssed. 4. Sterically stabilized microspheres may have potential for re- examining the microcirculatory pathways in healthy spleen and various splenomegalies.