Summary
Rats were injected intravenously with liposomes of various compositions and sizes
and blood platelet count measured. It was found that negatively-charged liposomal
systems produced a transient reduction in platelet count in the first 5 minutes after
injection which recovered by 60 minutes post-injection. This effect was most striking
for multilamellar vesicles (MLV’s) containing phosphatidylglycerol (PG). Dose levels
of 25 mg/kg of MLV’s containing 10 mole% PG caused the platelet count to drop from
a control value of 1,086 ± 21 × 109/1 to 193 ± 14 × 109/1 by 2 minutes post-injection, an 82% decline. This thrombocytopenic effect was observed
to diminish as vesicle size or vesicle dose was decreased. Positively-charged liposomes
produced a less pronounced transient reduction in platelet count while neutral liposomes
caused only a mild, transient platelet decline. This transient thrombocytopenic effect
was not blocked by common anticoagulants and fibrinolytic agents but was pi evented
by liposomal pretreatment. Radiolabeled platelet studies revealed that transient sequestration
of platelets occurs in the liver and spleen 2 minutes after PG :EPC:CHOL MLV injection
with a normalization of platelet distribution by 60 minutes post-injection. In vitro
studies, using an automated blood counter suggest a transient association of liposomes
and platelets occurring following injection. Liposomally-induced transient thrombocytopenia
suggests a role for platelets in the biodistribution of liposomes.
Keywords
Liposomes - Platelets - Biodistribution - Transient thrombocytopenia
