TY - JOUR
T1 - Kinetics of liposome-encapsulated hemoglobin after 25% hypovolemic exchange transfusion
AU - Awasthi, V. D.
AU - Garcia, D.
AU - Klipper, R.
AU - Phillips, W. T.
AU - Goins, B. A.
N1 - Funding Information:
This work was supported by a grant (Award number N00140010793) from the Office of Naval Research, Washington, DC (USA).
Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2004/9/28
Y1 - 2004/9/28
N2 - 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.
AB - 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.
KW - Blood substitute
KW - Exchange transfusion
KW - Liposome-encapsulated hemoglobin
KW - Liposomes
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U2 - 10.1016/j.ijpharm.2004.06.015
DO - 10.1016/j.ijpharm.2004.06.015
M3 - Article
C2 - 15363501
AN - SCOPUS:4444315484
VL - 283
SP - 53
EP - 62
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -