Kinetics of liposome-encapsulated hemoglobin after 25% hypovolemic exchange transfusion.
Liposome-encapsulated hemoglobin (LEH) is being developed as an oxygen therapeutic. In this work, we evaluated a neutral formulation of PEGylated LEH for its circulation and distribution properties in rodent models of 25% hypovolemic exchange transfusion. About 25% of blood in rats and rabbits was exchanged with LEH that had been previously labeled with 99mTc radionuclide. The distribution of 99mTc-LEH was followed by gamma camera imaging and intermittent blood sampling during 48 h, and counting the tissue-associated radioactivity after necropsy at 48 h. On the basis of circulation kinetics, the half-life of 99mTc-LEH in blood was 30 and 39.8 h in rats and rabbits, respectively. Apart from blood, major organs of accumulation of LEH after 48 h included liver (rats, 10.3% and rabbits, 5.4% of injected dose) and spleen (rats, 2.4% and rabbits, 0.8% of injected dose). The results demonstrate that LEH circulates for a prolonged time after administration and that the animals tolerate at least 25% of blood exchange without any distress. Subsequent to the enhanced uptake in the RES, the rats clear LEH from the circulation faster than the rabbits.
Awasthi
V D
VD
Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. awasthi@uthscsa.edu
Garcia
D
D
Klipper
R
R
Phillips
W T
WT
Goins
B A
BA
D000818:Animals; D016913:Blood Component Transfusion / Q000379:methods*; D006207:Half-Life; D006454:Hemoglobins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020896:Hypovolemia / Q000628:therapy*; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D006454:Hemoglobins; D008081:Liposomes