Polyethylene glycol (PEG)-grafted
phosphatidylcholine liposomes are used as
drug carriers due to their low immunogenicity and prolonged circulation time. The interaction between sterically stabilized
lecithin liposomes and platelets has not been investigated before, and deserves to be subjected to scrutiny inasmuch as the uptake of
liposomes by platelets could be detrimental for
drug delivery and primary hemostasis. Consequently, the interaction between resting and
convulxin-activated hamster and human platelets and
calcein- or 5,6-carboxyfluorescein-encapsulating PEGylated
liposomes composed of distearoyl- and
dipalmitoyl phosphatidylcholine and PEG-derivatized distearoyl
phosphatidylethanolamine was investigated by flow cytometry, confocal microscopy, and a glass capillary
thrombosis model. Fluorescently labeled
liposomes of the same composition were subsequently assayed in vivo after 15 and 45 min of systemic circulation. Neither resting nor activated hamster and human platelets interacted with
liposomes at 0.70 mM
lipid concentration. An absence of any interaction was corroborated in the in vivo experiments. Alternatively, flow cytometry assays evinced that human platelets interact with
liposomes at
lipid concentrations of >or=1.35 mM. These interactions were more profound for activated platelets than resting platelets. We conclude that the use of PEGylated
lecithin liposomes at
lipid concentrations of <1.35 mM has no detrimental impact on liposomal
drug delivery based on PEGylated
lecithin liposomes, but that these
drug carriers may be associated with a reduced targeting efficacy or compromised primary
hemostatic system when used at concentrations of >or=1.35 mM. In contrast, these
drug carriers may become valuable in
thrombosis- and
drug delivery-related research and applications at concentrations of >or=1.35 mM.