Wt. Phillips et al., Polyethylene glycol-modified liposome-encapsulated hemoglobin: A long circulating red cell substitute, J PHARM EXP, 288(2), 1999, pp. 665-670
Citations number
39
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
A major obstacle in the development of red cell substitutes has been overco
ming their short circulation persistence. In this study, distearoyl phospho
ethanolamine polyethylene glycol 5000 (PEG-PE) (10 mol%) was added to the f
ormulation of liposome-encapsulated hemoglobin (LEH) to decrease reticuloen
dothelial system uptake and prolong LEH circulation persistence. PEG-LEH wa
s radiolabeled with technetium, 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 coll
ected for counting in a scintillation well counter. Tissue distribution dat
a at 48 h revealed that 51.3 +/- 3.4% of the technetium-99m-PEG-LEH remaine
d in circulation, a greater than 3-fold increase in the circulation half-li
fe compared with circulation half-lives previously reported for non-PEG-con
taining 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 greatl
y prolongs the circulation persistence of LEH and represents a significant
step in the development of red cell substitutes with prolonged oxygen deliv
ery.