Abstract
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.
Footnotes
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Send reprint requests to: Dr. William Phillips, Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78284. E-mail:phillips{at}uthscsa.edu
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↵1 This work was supported by National Institutes of Health Grant RO1-HL53052, US Naval Medical Research and Development Command, and US Army Medical Research and Development Command (for supplying hemoglobin).
- Abbreviations:
- LEH
- liposome-encapsulated hemoglobin
- PEG
- polyethylene glycol
- DSPE
- distearoyl phosphoethanolamine
- 99mTc
- technetium-99m
- HMPAO
- hexamethylpropyleneamine oxime
- % ID
- percentage of injected dose
- RES
- reticuloendothelial system
- PEG-LEH
- polyethylene glycol-coated liposome-encapsulated hemoglobin
- DMPG
- dimyristoyl phosphatidylglycerol
- Received March 5, 1998.
- Accepted September 9, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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