Assessment of thrombogenic potential of liposomes.
The effects of liposomes with positive, neutral and negative surface charges on platelets and the plasmatic coagulation system were investigated in several in vitro and in vivo models. Negatively charged liposomes stimulated the plasmatic contact activating system as demonstrated by significant acceleration of whole blood clotting time measured in containers with nonwettable (siliconized) surface. The same liposomes induced reversible aggregates of human platelets in vitro and circulating reversible platelet aggregates after intravenous infusion in guinea pigs. Liposomes with positive and neutral surface charges had no effect on plasmatic coagulation and platelets. The biological mechanisms and the toxicological relevance of these findings are discussed.
Zbinden
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G
Institute of Toxicology, Swiss Federal Institute of Technology, ETH, Zurich, Switzerland.
Wunderli-Allenspach
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H
Grimm
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L
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D004563:Electrochemistry; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008081:Liposomes / Q000008:administration & dosage / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D013499:Surface Properties; D014914:Whole Blood Coagulation Time
D008081:Liposomes