Oral administration of recombinant human erythropoietin in liposomes in rats: influence of lipid composition and size of liposomes on bioavailability.
Intestinal absorption of recombinant human erythropoietin (Epo) encapsulated in liposomes (Epo/liposomes) was examined by measuring the pharmacological effects of Epo after oral administration in rats. Circulating reticulocyte counts after oral administration of Epo/liposomes showed a profile different from that after intravenous administration. Epo/liposomes 0.1 micron in diameter were absorbed more effectively than those 0.2 micron in diameter. In the 0.1 micron Epo/liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and soybean-derived sterols (SS), cholesterol (Ch), or soybean-derived sterylglucosides (SG), DPPC/SS (in molar ratio 7/2) and DPPC/Ch (7/2) showed higher efficiency in intestinal absorption than DPPC/Ch (7/4) and DPPC/SG (7/2) at a low dose by the sysmex method. Pharmacological availabilities for oral administration of Epo/liposomes were 0.74-31% and 3.3-30% as evaluated by circulating reticulocyte counts and percentage circulating reticulocytes of erythrocytes, respectively, in comparison to those for intravenous administration of the same dose.
Maitani
Y
Y
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Hazama
M
M
Tojo
Y
Y
Shimoda
N
N
Nagai
T
T
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000818:Animals; D001682:Biological Availability; D004906:Erythrocyte Count / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013025:Glycine max; D013261:Sterols / Q000737:chemistry*
D008081:Liposomes; D011994:Recombinant Proteins; D013261:Sterols; D004921:Erythropoietin; D015060:1,2-Dipalmitoylphosphatidylcholine