Pharmacokinetic properties and in-vivo biological activity of recombinant human erythropoietin encapsulated in red blood cells.
The in-vivo survival of 51Cr-labelled murine red blood cells (RBCs) loaded with recombinant human erythropoietin (rhEpo-RBCs) was slightly lower than that of normal RBCs. Intravenous administration to normal mice of the encapsulated rhEpo shows the pharmacokinetic bicompartmental profile typical of the free rhEpo. Distribution and elimination half-life values for the RBC-entrapped rhEpo were no longer than those for the free protein. The area under the curve value was significantly increased for rhEpo-RBCs. Hypertransfused polycythaemic mice were evaluated as an adequate animal model to study the in vivo biological activity of encapsulated rhEpo. rhEpo-RBCs stimulate the erythropoiesis of polycythaemic mice in a linear dose-radio-iron incorporation response relationship. These results suggest that rhEpo-RBCs may behave as an alternative to the administration of free rhEpo in the clinical field.
Garin
M I
MI
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Madrid, Spain.
López
R M
RM
Luque
J
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D004905:Erythrocyte Aging / Q000187:drug effects; D004912:Erythrocytes; D004921:Erythropoietin / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D011086:Polycythemia / Q000097:blood*; D011994:Recombinant Proteins
D004337:Drug Carriers; D011994:Recombinant Proteins; D004921:Erythropoietin