Nanoerythrosomes, a new derivative of erythrocyte ghost II: identification of the mechanism of action.
We have recently developed a new drug which is a carrier from red blood cell membrane. This carrier, named nanoerythrosome (nEryt), is prepared by extrusion of erythrocyte ghosts to produce small vesicles having an average diameter of 100 nm. Daunorubicin (DNR) was covalently conjugated to the nEryt (nEryt-DNR) using glutaraldehyde as homobifunctional linking arm. This led to a complex that is more active than free DNR both in vitro and in vivo. In this study, we identified the mechanisms that make the complex nEryt-DNR more active than free DNR. Using fluorescence microscopy and cellular-uptake, we observed that the nEryt-DNR complex cannot diffuse through the cell membrane and do not enter the cell by endocytosis. Our results suggest that the nEryt-DNR is rapidly absorbed onto the cell membrane. Free DNR is then slowly released by hydrolysis of the glutaraldehyde linking arm, producing a high concentration of free DNR in the cell's vicinity over a long period of time.
Département de Chimie-Biologie, Université du Québec à Trois-Rivières, Canada.
M
M
Moorjani
A
A
Lejeune
C
C
Gicquaud
J
J
Lacroix
P
P
Poyet
R C
RC
Gaudreault
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003630:Daunorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004910:Erythrocyte Membrane; D007941:Leukemia P388 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D003630:Daunorubicin