Abstract
Liposome-encapsulated hemoglobin (LEH) is being developed at the Naval Research Laboratory as a universally transfusable oxygen-carrying blood replacement. A chemical engineering scale-up feasibility study has been completed recently. We report here the development of an encapsulation method which produces liters of phospholipid/cholesterol liposomes containing at least 16 g% hemoglobin in a few hours. The 0.2 micron liposomes are produced with a MicrofluidizerTM (Microfluidics Corp., Newton, MA) adapted for this purpose, and then washed and sterile filtered using a Pellicon (Millipore, Bedford, MA) tangential flow filtration device. Previously, production limitations and lack of sterility have been serious barriers to toxicity testing for all the researchers engaged in related investigations. The biophysical properties of the LEH thus produced are ideal for use as a blood substitute, resembling those of red blood cells. The oxygen-binding affinity of LEH can be maintained at the level of fresh whole blood for many weeks by co-encapsulation of pyridoxal-5-phosphate. The circulation persistence time of liposomes is a function of the type of phospholipid. We have developed a formulation which has a circulation persistence time of 15–20 hours. The LEH oxygen binding characteristics, circulation half-life and its lipid composition dependence, scale-up preparation method, and a sterilization method are presented.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
“Criteria of Satisfactory Plasma Volume Expanders,” National Academy of Sciences, National Research Council, Washington DC (1963).
U.F. Gruber, “Blood Replacement,” Springer-Verlag, Berlin (1969).
“Blood Substitutes and Plasma Expanders, G.A. Jamieson and T.J. Greenwalt, eds., Alan R. Liss, Inc., New York (1978).
“Advances in Blood Substitute Research,” R.B. Bolin, R.P. Geyer and G.J. Nemo, eds., Alan R. Liss, Inc., New York (1983).
S.A. Gould, A.L. Rosen, L.R. Sehgal, H.L. Sehgal, L.A. Langdale, L.M. Krause, C.L. Rice, W.H. Chamberlin, and G.S. Moss, New England Journal of Medicine 314:1653 (1986).
R.K. Spence, S. McCoy, E.D. Norcross, J. Popovich, C.B. Jacobus, M.J. Pello, J.A. Alexander, R.C. Camishon, Biomat. Art. Cells. Art. Org. 15:436 (1987).
J.P. Savitsky, J. Doczi, J. Black, and J.D. Arnold, Clin. Pharmacol. Ther. 23:73 (1978).
W.M. Vogel, R.C. Dennis, G. Cassidy, C.S. Apstein, and C.R. Valeri, Am, J. Physiol. (Heart, Circ. Physiol), 20:H413 (1986).
T.M.S. Chang, Science 146:524 (1964).
T.A. Davis, W.J. Asher, and H.W. Wallace, Appl. Biochem. Biotech. 10:123 (1984).
M.C Levy, P. Rambourg, J. Levy, and G. Potron, J. Pharmaceut. Sci. 71:759 (1982).
M. Arakawa, A. Kato, and T. Kondo, Appl. Biochem. Biotech. 10:143 (1984).
J.A. Hayward, D.M. Levine, L. Neufeld, S.R. Simon, D.S. Johnston, and D. Chapman, FEBS Letters 187:261 (1985).
M. Ndong-Hkoume, P. Labrude, J.C. Humbert, B. Teisseire, and C. Vigneron, Annales Pharmaceut. Franc. 39:247 (1981).
E. Tsuchida, H. Nishide, M. Yuasa, and M. Sekine, Bull. Chem. Soc. Japan. 57:776 (1984).
E. Tsuchida and H. Nishide, in Biomimetic and Bioorganic Chemistry (II) Chapter 2. Springer Verlag, Berlin, N.Y. (1986).
L. Djordjevich and I.F. Miller, Exp. Hematol. 8:584 (1980).
C.A. Hunt and R.R. Burnette, in: Advances in Blood Substitute Research,” R.B. Bolin, R.P. Geyer, and G.J. Nemo, eds., Alan R. Liss, Inc., New York (1983).
B.P. Gaber, P. Yager, J.P. Sheridan, and E.L. Chang, FEBS Letters 153:285 (1983).
B.P. Gaber and M.C. Farmer, in “The Red Cell: Sixth Ann Arbor Conference,” G.J. Brewer, ed., Alan R. Liss, Inc., New York (1984).
M.C. Farmer, B.P. Gaber, and E.L. Chang, Biophvs. J. 41:191a (1983).
F. Olson, C.A. Hunt, F.C Szoka, W.J. Vail, and D. Papahadjopoulos, Biochem. Biophys. Acta 557:9 (1979).
M.C. Farmer and B.P. Gaber, Methods in Enzymology 149:184 (1987).
R.L. Beissinger, M.C. Farmer, and J.L. Gossage, Trans. Am. Soc. Artif.Intern. Organs 32:58 (1986).
E. Mayhew, R. Lazo, W.J. Vail, J. King, and A.M. Green, Biochem. Biophys. Acta 775:169 (1984).
C. Nicolau, B.P. Teisseire, C. Ropass, M-O Valiez, and R.A. Herigault, Biblthca Haemat. 51:92 (1985).
K. Vandegriff and J. Olson, J Biol Chem. 259:12619 (1984).
C.A. Hunt, R.R. Burnette, R.D. MacGregor, A.E. Strubbe, D.T. Lau, N. Taylor, and H. Kawada, Science 30:1165 (1985).
J. Senior and G. Gregoriadis, Life Sciences 30:2123 (1982).
S. Mabrey-Gaud, in: Liposomes: From Physical Structure to Therapeutic Applications,” C.G. Knight, ed., Elsevier/North Holland, Amsterdam (1981).
M.C. Farmer, and S.A. Johnson, Biophy. J. 49:139a (1986).
A. Schmidt, Pflug. Arch. Ges. Phvsiol. 11:515 (1875).
E.C. Richardson, B. Banerji, R.C. Seid, Jr., R. Levin, and C.R. Alving, Infection and Immunity 39:1385 (1983).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Plenum Press, New York
About this chapter
Cite this chapter
Farmer, M.C., Johnson, S.A., Beissinger, R.L., Gossage, J.L., Lynn, A.B., Carter, K.A. (1988). Liposome-Encapsulated Hemoglobin: A Synthetic Red Cell. In: Gaber, B.P., Schnur, J.M., Chapman, D. (eds) Biotechnological Applications of Lipid Microstructures. Advances in Experimental Medicine and Biology, vol 238. Springer, New York, NY. https://doi.org/10.1007/978-1-4684-7908-9_13
Download citation
DOI: https://doi.org/10.1007/978-1-4684-7908-9_13
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4684-7910-2
Online ISBN: 978-1-4684-7908-9
eBook Packages: Springer Book Archive