Nanoerythrosomes, a new derivative of erythrocyte ghost: III. Is phagocytosis involved in the mechanism of action?

We have previously developed a new drug carrier, named nanoerythrosome which is prepared by extrusion of erythrocyte ghosts to produce small vesicles having an average diameter of 100 nm. Daunorubicin (DNR) conjugated to these nanoerythrosomes has a higher antineoplastic index than the free drug. Moreover, since nanoerythrosomes are particles, phagocytosis may be involved in their mechanism of potentiation. In the present study, we have compared the mechanism of penetration between free DNR and conjugate DNR linked to nanoerythrosomes, on cells presenting high phagocytic activity, macrophages, and cells lacking phagocytic activity, the P388 D1 cell line. Our results demonstrate that: 1) The nanoerythrosome-DNR complex is rapidly adsorbed and phagocytosed by the macrophages, but not by the P388 D1 cell line. 2) On the contrary, DNR enters both phagocytic and non phagocytic cells. Furthermore, the cellular distribution of DNR is the same in both cell lines, the nucleus being the target organelle. We conclude that phagocytosis of the nanoerythrosome-DNR complex is not involved in its mechanism of action.