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 e...

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Bibliographic Details
Published in:International journal of pharmaceutics 2004-09, Vol.283 (1), p.53-62
Main Authors: Awasthi, V.D., Garcia, D., Klipper, R., Phillips, W.T., Goins, B.A.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Blood Component Transfusion - methods
Blood substitute
Exchange transfusion
General pharmacology
Half-Life
Hemoglobins - administration & dosage
Hemoglobins - pharmacokinetics
Hypovolemia - therapy
Liposome-encapsulated hemoglobin
Liposomes
Liver - metabolism
Male
Medical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Rabbits
Rats
Rats, Sprague-Dawley
Spleen - metabolism
Tissue Distribution
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Summary: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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2004.06.015