Circulation kinetics and organ distribution of Hb-vesicles developed as a red blood cell substitute

Keitaro Sou, Robert Klipper, Beth Goins, Eishun Tsuchida, William T Phillips

Research output: Contribution to journalArticle

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Abstract

Phospholipid vesicles encapsulating concentrated human hemoglobin (Hb-vesicles, HbV), also known as liposomes, have a membrane structure similar to that of red blood cells (RBCs). These vesicles circulate in the bloodstream as an oxygen carrier, and their circulatory half-life times (t1/2) and biodistribution are fundamental characteristics required for representation of their efficacy and safety as a RBC substitute. Herein, we report the pharmacokinetics of HbV and empty vesicles (EV) that do not contain Hb, in rats and rabbits to evaluate the potential of HbV as a RBC substitute. The samples were labeled with technetium-99m and then intravenously infused into animals at 14 ml/kg to measure the kinetics of HbV elimination from blood and distribution to the organs. The t1/2 values were 34.8 and 62.6 h for HbV and 29.3 and 57.3 h for EV in rats and rabbits, respectively. At 48 h after infusion, the liver, bone marrow, and spleen of both rats and rabbits had significant concentrations of HbV and EV, and the percentages of the infused dose in these three organs were closely correlated to the circulatory half-life times in elimination phase (t1/2β). Furthermore, the milligrams of HbV per gram of tissue correlated well between rats and rabbits, suggesting that the balance between organ weight and body weight is a fundamental factor determining the pharmacokinetics of HbV. This factor could be used to estimate the biodistribution and the circulation time of HbV in humans, which is estimated to be equal to that in rabbit.

Original languageEnglish (US)
Pages (from-to)702-709
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume312
Issue number2
DOIs
StatePublished - Feb 2005

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Blood Substitutes
Erythrocytes
Rabbits
Half-Life
Pharmacokinetics
Organ Size
Technetium
Liposomes
Phospholipids
Hemoglobins
Spleen
Bone Marrow
Body Weight
Oxygen
Safety
Membranes
Liver

ASJC Scopus subject areas

  • Pharmacology

Cite this

Circulation kinetics and organ distribution of Hb-vesicles developed as a red blood cell substitute. / Sou, Keitaro; Klipper, Robert; Goins, Beth; Tsuchida, Eishun; Phillips, William T.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 312, No. 2, 02.2005, p. 702-709.

Research output: Contribution to journalArticle

Sou, Keitaro ; Klipper, Robert ; Goins, Beth ; Tsuchida, Eishun ; Phillips, William T. / Circulation kinetics and organ distribution of Hb-vesicles developed as a red blood cell substitute. In: Journal of Pharmacology and Experimental Therapeutics. 2005 ; Vol. 312, No. 2. pp. 702-709.
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