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Interactions of liposomes and platelets
L W Reinish1, M B Bally, H C Loughrey
1University of British Columbia, Faculty of Medicine, Department of Biochemistry, Vancouver, Canada.
Abstract:
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 X 10(9)/l to 193 +/- 14 X 10(9)/l 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 prevented 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.
Insights
Negatively-charged liposomes, particularly those with phosphatidylglycerol, transiently reduce rat platelet counts. This effect, most pronounced with larger vesicles, suggests platelets play a role in liposome biodistribution.
Area of Science:
- Pharmacology
- Biotechnology
- Nanomedicine
Background:
- Liposomes are widely investigated drug delivery systems.
- Understanding liposome-biomolecule interactions is crucial for optimizing in vivo performance.
- Platelet count changes after liposome administration are not fully understood.
Purpose of the Study:
- To investigate the effect of liposome charge and composition on blood platelet count in rats.
- To elucidate the mechanism behind liposome-induced transient thrombocytopenia.
- To explore the role of platelets in liposome biodistribution.
Main Methods:
- Intravenous injection of liposomes with varying compositions and sizes into rats.
- Measurement of blood platelet counts at different time points post-injection.
- Use of radiolabeled platelets to track their distribution.
- In vitro studies using automated blood counters to assess liposome-platelet association.
Main Results:
- Negatively-charged liposomes, especially multilamellar vesicles (MLVs) with phosphatidylglycerol (PG), caused a significant transient decrease in platelet count.
- The thrombocytopenic effect diminished with decreasing vesicle size or dose.
- Radiolabeled platelet studies showed transient sequestration in the liver and spleen.
- In vitro studies suggested a transient association between liposomes and platelets.
Conclusions:
- Liposome charge significantly influences transient thrombocytopenia.
- Platelet sequestration in the liver and spleen appears to be the primary cause of the observed reduction in circulating platelets.
- These findings suggest a role for platelets in the in vivo biodistribution of liposomes.