Chronic liposome administration in mice: effects on reticuloendothelial function and tissue distribution.
Liposomes have a pronounced tendency to localize in the reticuloendothelial (RE) system, a major host defense system. We have examined, in mice, the effect of chronic i.v. administration of low to moderate liposome doses on drug metabolism, phagocytic index and spleen and liver size. Little effect on the rate of pentobarbital metabolism was noted, except when mice received 80 mg/kg of sphingomyelin-containing liposomes in a series of 10 injections over 3.5 weeks. Impairment of RE phagocytic function was found to be related to liposome size and composition, size and frequency of liposome dose and the presence of lipid peroxides. The effects on tissue distribution of liposome-entrapped [14C]sucrose was also determined in mice receiving chronic liposome injections. In RE blockaded mice there was a consistent trend in favor of decreased liver uptake and increased spleen uptake. No significant uptake of liposome contents was seen in non-RE tissues even in mice with severe RE blockade, indicating that the induction of RE blockade by predosing with empty liposomes may not be a successful strategy for increasing liposome uptake to non-RE tissues. Liver to spleen ratios of [14C]sucrose appeared to be a sensitive method for quantitating RE blockade. Sphingomyelin-containing liposomes produced the greatest RE blockade, distearoylphosphatidylcholine-cholesterol liposomes were intermediate and egg phosphatidylcholine-cholesterol liposomes produced the least impairment in RE function. Liposomes which contained 1% vitamin E as an antioxidant had slightly less effect on RE function than liposomes not containing vitamin E.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002784:Cholesterol; D005260:Female; D007275:Injections, Intravenous; D008081:Liposomes / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D012157:Mononuclear Phagocyte System / Q000187:drug effects*; D010587:Phagocytosis; D010714:Phosphatidylethanolamines; D013395:Sucrose / Q000378:metabolism; D014018:Tissue Distribution
D008081:Liposomes; D010714:Phosphatidylethanolamines; D013395:Sucrose; D002784:Cholesterol