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Vol. 288, Issue 2, 665-670, February 1999

Polyethylene Glycol-Modified Liposome-Encapsulated Hemoglobin: A Long Circulating Red Cell Substitute1

W. T. Phillips, R. W. Klipper, V. D. Awasthi, A. S. Rudolph, R. Cliff, V. Kwasiborski and B. A. Goins

Radiology Department, University of Texas Health Science Center at San Antonio, San Antonio, Texas (W.T.P., R.W.K., V.D.A., B.A.G.); and Center for BioMolecular Science and Engineering, Naval Research Laboratory, Washington, DC (A.S.R., R.C., V.K.)

A major obstacle in the development of red cell substitutes has been overcoming their short circulation persistence. In this study, distearoyl phosphoethanolamine polyethylene glycol 5000 (PEG-PE) (10 mol%) was added to the formulation of liposome-encapsulated hemoglobin (LEH) to decrease reticuloendothelial system uptake and prolong LEH circulation persistence. PEG-LEH was radiolabeled with technetium-99m, infused into rabbits (25% of blood pool at 1 ml/min) (n = 5), and monitored by scintigraphic imaging at various times out to 48 h. At 48 h, animals were sacrificed, and tissue samples were collected for counting in a scintillation well counter. Tissue distribution data at 48 h revealed that 51.3 ± 3.4% of the technetium-99m-PEG-LEH remained in circulation, a greater than 3-fold increase in the circulation half-life compared with circulation half-lives previously reported for non-PEG-containing LEH formulations. The liver had the greatest accumulation at 48 h (12.7 ± 0.7%), followed by bone marrow (6.2 ± 0.1%), whereas the spleen had only 1.4 ± 0.2%. The addition of PEG-PE to the LEH formulation greatly prolongs the circulation persistence of LEH and represents a significant step in the development of red cell substitutes with prolonged oxygen delivery.

0022-3565/99/2882-0665$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


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