Delivery to macrophages and toxic action of etoposide carried in mouse red blood cells.
Erythrocytes could be used as physiological carriers of active compounds. Several substances can be loaded into erythrocytes by hypotonic dialysis methods. Furthermore, carrier erythrocyte membrane can be chemically modified in order to promote increased arrival of the loaded compound to macrophages. In this work, we have prepared erythrocytes loaded with etoposide. We found conditions to obtain high etoposide encapsulation yields with minor alteration of some cell parameters of these carrier erythrocytes. Etoposide loaded into erythrocytes is mainly localised in the cytoplasmic compartment. Membrane modification of etoposide-loaded erythrocytes with band 3 crosslinkers produces an increased incorporation of the drug into macrophages mainly by phagocytosis process. The toxic effect of etoposide conveyed in these carrier erythrocytes determined as DNA fragmentation in macrophages was higher than that shown by free etoposide added at the same concentration in the culture medium to macrophages. These results seem to indicate the usefulness of this model to deliver this anti-tumour compound to macrophages, which might be useful in therapy.
Lotero
L Alfredo
LA
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid E-28871, Spain.
Olmos
Gemma
G
Diez
José C
JC
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004912:Erythrocytes; D005047:Etoposide / Q000008:administration & dosage* / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D010587:Phagocytosis; D014316:Tritium
D000970:Antineoplastic Agents; D004337:Drug Carriers; D014316:Tritium; D005047:Etoposide