Effect of splenic congestion associated with haemolytic anaemia on filtration of 'spleen-homing' microspheres.
1. The surface of large model 125I-labelled polystyrene microspheres (220 nm in diameter) was coated with the polyoxyethylene/polyoxypropylene block co-polymer poloxamine-908. The coated microspheres were injected intravenously into rats. Up to 40% of the administered dose had accumulated 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 in the liver uptake. In contrast, smaller poloxamine-908-coated microspheres (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 haemolytic anaemia, on filtration of poloxamine-908-coated microspheres was studied. The enlarged spleen of the anaemic rats was incapable of efficiently 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. However, the splenic filtration of large coated microspheres was still five-fold higher than that of uncoated microspheres of similar size in anaemic animals. 3. The potential use of large sterically stabilized colloids and drug carriers for selective spleen scanning and splenic drug delivery in pathological conditions, where anaemia prevails, is discussed. 4. Sterically stabilized microspheres may have potential for re-examining the microcirculatory pathways in healthy spleen and various splenomegalies.
Moghimi
S M
SM
Department of Pharmaceutical Sciences, University of Nottingham, U.K.
Hedeman
H
H
Illum
L
L
Davis
S S
SS
D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D003102:Colloids; D004337:Drug Carriers / Q000493:pharmacokinetics; D005029:Ethylenediamines / Q000493:pharmacokinetics; D005374:Filtration; D008297:Male; D008863:Microspheres; D010659:Phenylhydrazines; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism*; D014018:Tissue Distribution
D003102:Colloids; D004337:Drug Carriers; D005029:Ethylenediamines; D010659:Phenylhydrazines; C030299:phenylhydrazine; C012571:tetronic 701; D011092:Polyethylene Glycols