Pharmacokinetic study of enclosed hemoglobin and outer lipid component after the administration of hemoglobin vesicles as an artificial oxygen carrier.
The hemoglobin vesicle (HbV) is an artificial oxygen carrier that encapsulates a concentrated Hb solution in lipid vesicles (liposomes). The pharmacokinetic properties of HbV were investigated in mice and rats. With use of HbV in which the internal Hb was labeled with (125)I ((125)I-HbV) and cell-free (125)I-Hb, it was found that encapsulation of Hb increased the half-life by 30 times, accompanied by decreased distribution in both the liver and kidney. The half-life of HbV was increased, and the uptake clearance for the liver and spleen were decreased with increasing doses of HbV. In an in vitro study, the specific uptake and degradation of HbV in RAW 264.7 cells were found, but this was not the case for parenchymal and endothelial cells. The pharmacokinetics of HbV components (internal Hb and liposomal lipid) were also investigated using (125)I-HbV and (3)H-HbV (liposomal cholesterol was radiolabeled with tritium-3). The time courses for the plasma concentration curves of (125)I-HbV, (3)H-HbV, and iron derived from HbV suggest that HbV maintain an intact structure in the blood circulation up to 24 h after injection. (125)I-HbV and (3)H-HbV were distributed mainly to the liver and spleen. Internal Hb disappeared from both the liver and spleen 5 days after injection, and the liposomal cholesterol disappeared at approximately 14 days. Internal Hb was excreted into the urine and cholesterol into feces via biliary excretion. These results suggest that the HbV has a reasonable blood retention and metabolic and excretion performance and could be used as an oxygen carrier.
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Kazuaki
K
Taguchi
Yukino
Y
Urata
Makoto
M
Anraku
Toru
T
Maruyama
Hiroshi
H
Watanabe
Hiromi
H
Sakai
Hirohisa
H
Horinouchi
Koichi
K
Kobayashi
Eishun
E
Tsuchida
Toshiya
T
Kai
Masaki
M
Otagiri
D000818:Animals; D001802:Blood Substitutes / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006207:Half-Life; D006454:Hemoglobins / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids; D008297:Male; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen
D001802:Blood Substitutes; D004337:Drug Carriers; D006454:Hemoglobins; D008055:Lipids; D010100:Oxygen