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Non-phospholipid Liposomes: A Novel Method for the Preparation of Hemoglobin Containing Lipid Vesicles

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Blood Substitutes

Abstract

Encapsulation of hemoglobin, the primary oxygen carrier, within a vesicle consisting of a semi-permeable membrane and an aqueous inner core may solve several of the problems presented by cell-free hemoglobin solutions. In anticipation of this, liposome-encapsulated hemoglobin products are now being actively developed as a second-generation red cell substitute (Rudolph 1995). The semi-permeable membrane permits free diffusion of gases between hemoglobin and tissues and provides a barrier that prevents large or charged molecules from moving across the membrane. These vesicles provide an efficient oxygen transport system by maintaining hemoglobin at a relatively high concentration within the membrane envelope, while isolating it from damaging components present in blood plasma and, conversely, protecting the endothelial tissue or blood components from cytotoxic effects of free hemoglobin molecules.

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References

  • Akama, K., K. Morizawa, S. Tokuyama, T. Satoh, K. Kobayashi, S. Sekiguchi, and E. Tsuchida. Oxygen transport and in vivo parameters of artificial red cells (ARC). Artif. Cells, Blood Substitutes, Immobil. Biotech. 22: 901–907, 1994.

    Article  CAS  Google Scholar 

  • Alayash, A.I., and R.E. Cashon. Hemoglobin and free radicals: implications for the development of a safe blood substitute. Molecular Medicine Today 1: 122–127, 1995.

    Article  PubMed  CAS  Google Scholar 

  • Allen, T.M. Stealth® liposomes: avoiding reticuloendothelial uptake. In Liposomes in the Therapy of Infectious Diseases and Cancer (G. Lopez-Berestein and I.J. Fidler, Eds.) New York: Alan R. Liss 1989, pp. 405–415.

    Google Scholar 

  • Azmin M.N., A.T. Florence, R.M. Handjani-Vila J.F. Stuart, G. Vanlerberghe G, and J.S. Whittaker. The effect of non-ionic surfactant vesicle (niosome) entrapment on the absorption and distribution of methotrexate in mice. J. Pharm. Pharmacol. 37: 237–242, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Bailie, A.J., A.T. Florence, L.R. Hume, G.T. Muirhead, and A. Rog-erson. The preparation of niosomes~non-ionic surfactant vesicles. Pharm. Pharmacol. 37: 863–868, 1985.

    Google Scholar 

  • Bangham, A.D., M.M. Standish, and J.C. Watkins. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol. 13: 238–252, 1965.

    Article  PubMed  CAS  Google Scholar 

  • Beissinger, R.L., M.C. Farmer, and J.L. Gossage. Liposome-encapsulated hemoglobin as a red cell surrogate. Trans. Am. Soc. Artif. Intern. Organs 32: 58–63, 1986.

    CAS  Google Scholar 

  • Berger, R.L., B. Balko, and H.F. Chapman. High resolution mixer for the study of the kinetics of rapid reactions in solution. Rev. Sci. Inst. 39: 493–498, 1968.

    Article  CAS  Google Scholar 

  • Blantz, R.C., A.P. Evan, and F.B. Gabbai. Red cell substitutes in the kidney. In Blood Substitutes: Physiological Basis of Efficacy (R.M. Winslow, K.D. Vandegriff and M. Intaglietta, Eds.) Boston: Birkhauser, 1995, pp. 132–142.

    Chapter  Google Scholar 

  • Chang, T.M.S. Hemoglobin corpuscles. Report of a research project of B.Sc. Honours Physiology, McGill University, Medical Library, Mclntyre Building, McGill University, 1957, pp. 1–25.

    Google Scholar 

  • Chang, T.M.S., F.C. Macintosh, and S.G. Mason. Semipermeable aqueous microcapsules: I. Preparation and properties. Can. J. Physiol. Pharmacol. 44: 115–128, 1966.

    Article  PubMed  CAS  Google Scholar 

  • Clerc, S.G., and T.E. Thompson. A possible mechanism for vesicle formation by extrusion. Biophys. J. 67: 475–477, 1994.

    Article  PubMed  CAS  Google Scholar 

  • Cliff, R.O., F. Ligler, B. Goins, P.M. Hoffman, H. Spielberg, and A.S. Rudolph. Liposome encapsulated hemoglobin: long term storage and stability. Biomat. Artif. Cells Immobil. Biotech. 20: 619–626, 1992.

    CAS  Google Scholar 

  • Djordevich, L., and I.F. Miller. Synthetic erythrocytes from lipid-encapsulated hemoglobin. Exp. Hematol. 8: 584–592, 1980.

    Google Scholar 

  • Domokos, G., B. Jopski, and K.-H. Schmidt. Preparation properties and biological function of liposome encapsulated hemoglobin. Biomat. Artif. Cells Immobil. Biotech. 20: 345–354, 1992.

    CAS  Google Scholar 

  • Farmer, M.C. and B.P. Gaber. Liposome-encapsulated hemoglobin as an artificial oxygen-carrying system. Meth. Enzymol. 149: 184–200, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Fendler, J. Membrane mimetic chemistry. New York: John Wiley Sons, 1982.

    Google Scholar 

  • Feola, M., J. Simoni, P.C. Canizaro, R. Tran, G. Raschbaum, and F.J. Behal. Toxicity of polymerized hemoglobin solutions. Surg. Gynecol. Obstet. 166: 211–222, 1988.

    PubMed  CAS  Google Scholar 

  • Gaber, B.P., P. Yager, J.P. Sheridan, and E.L. Chang. Encapsulation of hemoglobin in phospholipid vesicles. FEBS Lett. 153: 285–288, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Gershfeld, N.L., CP. Mudd, K. Tajima, and R.L. Berger. Critical temperature for unilamellar vesicle formation in dimyristoylphosphati-dylcholine dispersions from specific heat measurements. Biophys. J. 65: 1174–1179, 1993.

    Article  PubMed  CAS  Google Scholar 

  • Gregoriadis, G. Drug entrapment in liposomes. FEBS Lett. 36: 292–296, 1973.

    Article  PubMed  CAS  Google Scholar 

  • Gregoriadis, G. Enzyme entrapment in liposomes. Meth. Enzymol. 44: 218–227, 1976.

    Article  PubMed  CAS  Google Scholar 

  • Hamilton, P.B., A* Miller, and D.D. Van Slyke. Renal effects of hemoglobin infusions in dogs in hemorrhagic shock. J. Exp. Med. 86: 477, 1947.

    Article  PubMed  CAS  Google Scholar 

  • Hargreaves, W.R., and D.W. Deamer. Liposomes from ionic, single chain amphiphiles. Biochemistry 17: 3759–3768, 1978.

    Article  PubMed  CAS  Google Scholar 

  • Hess, J.R., V.W. Macdonald, C.S. Gomez, and V. Coppes. Increased vascular resistance with hemoglobin-based oxygen carriers. Artif. Cells, Blood Substitutes, Immobil. Biotech. 22: 361–372, 1994.

    Article  CAS  Google Scholar 

  • Hunt, CA., R.R. Burnette, R.D. MacGregor, A.E. Strubbe, D.T. Lau, N. Taylor, and H. Kawada. Synthesis and evaluation of a prototypal artificial red cell. Science 230: 1165–1168, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Kaca, W., R.L Roth, and J. Levin. Hemoglobin, a newly recognized lipopolysaccharide (LPS) binding protein which enhances LPS biological activity. Artif. Cells, Blood Substitutes, Immobil. Biotech. 22: 387–398, 1994.

    Article  Google Scholar 

  • Kugiyama, K., SA. Kerns, J.D. Morrisett, R. Roberts, and P.D. Henry. Impairment of endothelium-dependent arterial relaxation by ly-solecithin in modified low-density lipoproteins. Nature 344: 160–2, 1990.

    Article  PubMed  CAS  Google Scholar 

  • LaBrake, C.C., and Fung, L.W.-M. Phospholipid vesicles promote human hemoglobin oxidation. J. Biol. Chem. 267: 16703–16711, 1992.

    PubMed  CAS  Google Scholar 

  • Lasic, D.D., F.J. Martin, A. Gabizon, S.K. Huang, and D. Papahad-jopoulos. Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times. Biochim. Biophys. Acta 1070: 187–192, 1991.

    Article  PubMed  CAS  Google Scholar 

  • Ligler, F.S., L.P. Stratton, and AS. Rudolph. Liposome encapsulated hemoglobin: stabilization, encapsulation and storage. InThe Red Cell: Seventh Ann Arbor Conference New York: Alan R. Liss, Inc., 1989, pp. 435–455.

    Google Scholar 

  • Manning, J.M. Design of chemically modified and recombinant hemoglobins as potential red cell substitutes. In Blood Substitutes: Physiological Basis of Efficacy (R.M. Winslow, K.D. Vandegriff and M. Intaglietta, Eds.) Boston: Birkhauser 1995, pp. 76–89.

    Chapter  Google Scholar 

  • Matsuda N., K. Nakai, M. Amano, TA. Takahashi, T. Ohta, I. Sakuma, A. Kitabatake, Y. Nakazato, and S. Sekiguchi. The quality control of stroma-free hemoglobin: lysophosphatidylcholine, a component of stromal phospholipids, as candidate vasoconstrictive factor. Artif. Cells, Blood Substitutes, Immobil. Biotech. 22: 939–944, 1994.

    Article  CAS  Google Scholar 

  • Nakai, K., N. Matsuda, M. Amano, T. Ohta, S. Tokuyama, K. Akama, Y. Kawakami, E. Tsuchida, and S. Sekiguchi. Acellular and cellular hemoglobin solutions as a vasoconstrictive factor. Artif. Cells, Blood Substitutes, Immobil. Biotech. 22: 559–564, 1994.

    Article  CAS  Google Scholar 

  • Panter, S.S., K.D. Vandegriff, P.O. Yan, and R.F. Regan. Assessment of hemoglobin-dependent neurotoxicity: alpha-alpha crosslinked hemoglobin. Artif. Cells, Blood Substitutes, Immobil. Biotech. 22: 399–413, 1994.

    Article  CAS  Google Scholar 

  • Papahadjopoulos, D. (Ed.) Ann. N.Y. Acad. Sci. 308, 1978.

    Google Scholar 

  • Philippot, J.R., S. Mutaftschiev, and J.P. Liatard. A very mild method allowing the encapsulation of very high amounts of macromole-cules into very large (1000 nm) unilamellar liposomes. Biochim. Biophys. Acta 734: 137–143, 1983.

    Article  CAS  Google Scholar 

  • Presti, F.T., and S.I. Chan. Cholesterol phospholipid interactions in membranes. I. Cholestane spin-label studies of phase behavior of cholesterol-phospholipid liposomes. Biochemistry 21: 3821–3830, 1982.

    Article  PubMed  CAS  Google Scholar 

  • Rudolph A.S., R.O. Cliff, R. Klipper, B. Goins, and W.T. Phillips. Circulation persistence and biodistribution of lyophilized liposome-encapsulated hemoglobin: an oxygen-carrying resuscitative fluid. Crit. Care Med. 22: 42–50, 1994.

    Google Scholar 

  • Rudolph, A.S. Encapsulated hemoglobin: current issues and future goals. Artif. Cells, Blood Substitutes, Immobil. Biotech. 22: 347–360, 1994.

    Article  CAS  Google Scholar 

  • Rudolph, A.S. Encapsulation of hemoglobin in liposomes. In Blood Substitutes: Physiological Basis of Efficacy (R.M. Winslow, K.D. Vandegriff and M. Intaglietta, Eds.) Boston: Birkhauser 1995, pp. 90–104.

    Chapter  Google Scholar 

  • Simoni, J., M. Feola, and P.C. Canizaro. Generation of free oxygen radicals and the toxicity of hemoglobin solutions. Biomat. Artif Cells Artif. Org. 18: 189–202, 1990.

    CAS  Google Scholar 

  • Smith, CD., S.T. Schuschereba, J.R. Hess, L. McKinney, D. Bunch, and P.D. Bowman. Liver and kidney injury after administration of hemoglobin cross-linked with bis(3,5-dibromosalicyl)fumarate. Biomat. Artif Cells Artif. Org. 18: 251–261, 1990.

    CAS  Google Scholar 

  • Surgenor, D.M., and D.F.H. Wallach. Biophysical aspects of platelet reaction mechanisms in clotting. In Henry Ford Hospital International Symposium, Blood Platelets. (S.A. Johnson, Ed.) Boston: Little Brown Co, 1961.

    Google Scholar 

  • Szebeni, J., CC Winterbourn, and R.W. Carrell. Oxidative interactions between hemoglobin and membrane lipid. A liposome model. Bio-chem. J. 220: 685–692, 1984.

    CAS  Google Scholar 

  • Szebeni, J., E.E. Di Iorio., H. Hauser, and K.H. Winterhalter. Encapsulation of hemoglobin in phospholipid liposomes: characterization and stability. Biochemistry 24: 2827–2832, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Szebeni, J., N.M. Wassef, H. Spielberg, A.S. Rudolph, and CR. Alving. Complement activation in rats by liposomes and liposomeencapsulated hemoglobin: evidence for anti-lipid antibodies and alternative pathway activation. Biochem. Biophys. Res. Comm. 205: 255–263, 1994.

    Article  PubMed  CAS  Google Scholar 

  • Szoka, F.C., F. Olson, T. Heath, W.J. Vail, E. Mayhew, and D. Pa-pahadjopoulos. Preparation of unilamellar liposomes of intermediate size (0.1–0.2 urn) by a combination of reverse phase evaporation and extrusion through polycarbonate membranes. Biochim. Biophys. Acta 601: 559–571, 1980.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, A. Characterization of neo red cells (NRC), their function and safety in vivo tests. Artif. Cells, Blood Substitutes, Immobil. Biotech. 23: 347–354, 1995.

    Article  CAS  Google Scholar 

  • Tanford, C. The Hydrophobic Effect. New York: John Wiley and Sons, 1980.

    Google Scholar 

  • Tsai, A.G., H. Kerger, and M. Intaglietta. Microcirculatory consequences of blood substitution with aoe-hemoglobin. In Blood Substitutes: Physiological Basis of Efficacy (R.M. Winslow, K.D. Vandegriff and M. Intaglietta, Eds.) Boston: Birkhauser 1995, pp. 155–174.

    Chapter  Google Scholar 

  • Tsuchida, E. Synthesis and characterization of artificial red cell (ARC). Biomat. Artif. Cells, Immobil. Biotech. 20: 337–344, 1992.

    CAS  Google Scholar 

  • Tsuchida, E. Stabilized hemoglobin vesicles. Artif. Cells, Blood Substitutes, Immobil. Biotech. 22: 467–477, 1994.

    Article  CAS  Google Scholar 

  • Usuba, A. and R. Motoki. Safety and efficacy of encapsulated hemoglobin in hemorrhagic shock. In Artificial Red Cells (E. Tsuchida, Ed.) Chichester: John Wiley Sons Ltd, 1995, pp. 65–92.

    Google Scholar 

  • Usuba, A, R. Motoki, K. Suzuki, K. Sakaguchi, and A. Takahashi. Study of effect of the newly developed “neo red cells” (NRC) on hemodynamics and blood gas transport in canine hemorrhagic shock. Biomat. Artif. Cells Artif. Org. 20: 531–535, 1992.

    CAS  Google Scholar 

  • Vandegriff, K.D., D.F.H. Wallach, and R.M. Winslow. Encapsulation of hemoglobin in non-phospholipid vesicles. Artif. Cells, Blood Substitutes, Immobil. Biotech. 22: 849–854, 1994.

    Article  CAS  Google Scholar 

  • Vivier, A., J.-C. Vuillemard, H.-W. Ackerman, and D. Poncelet. Large-scale blood substitute production using a microfluidizer. Biomat. Artif. Cells Immobil. Biotech. 20: 377–397, 1992.

    CAS  Google Scholar 

  • Wallach, D.F.H., PA Maurice, BA. Steele, and D.M. Surgenor. Studies on the relationship between the colloidal state and the clot-promoting activity of pure phosphatidylethanolamines. J. Biol. Chem. 234: 2829–2834, 1959.

    CAS  Google Scholar 

  • Wallach, D.F.H., and J.R. Philippot. In Liposome Technology 2 Edition (G. Gregoriadis, Ed.) Boca Raton: CRC Press, 1993, pp. 141–156.

    Google Scholar 

  • Wallach, D.F.H., and C. Yiournas. Method and apparatus for producing lipid vesicles. U.S. Patent Number 5,013,497, 1990.

    Google Scholar 

  • White, C.T., A.J. Murray, D.J. Smith, J.R. Greene, and R.B. Bolin. Synergistic toxicity of endotoxin and hemoglobin. J. Lab. Clin. Med. 108: 132–137, 1986.

    PubMed  CAS  Google Scholar 

  • Winslow, R.M. Hemoglobin-based Red Cell Substitutes. Baltimore: Johns Hopkins University Press, 1992.

    Google Scholar 

  • Winterhalter, M., and D.D. Lasic. Liposome stability and formation: experimental parameters and theories on the size distribution. Chem. Phys. Lipids 64: 35–43, 1993.

    Article  PubMed  CAS  Google Scholar 

  • Woodle, M.C., and D.D. Lasic. Sterically stabilized liposomes. Bio-chim. Biophys. Acta 1113: 171–199, 1992.

    CAS  Google Scholar 

  • Yoshida, Y., K. Kashiba, and E. Niki. Free radical-mediated oxidation of lipids induced by hemoglobin in aqueous dispersions. Biochim. Biophys. Acta 1201: 165–172, 1994.

    PubMed  CAS  Google Scholar 

  • Zheng, S., Y. Zheng, R. Beissinger, and R. Fresco. Liposome-encapsulated hemoglobin processing methods. Biomat. Artif. Cells Immobil. Biotech. 20: 355–364, 1992.

    CAS  Google Scholar 

  • Zheng, S., Y. Zheng, and R. Beissinger. Efficacy, physical properties and pharmacokinetics of sterically-stabilized liposome encapsulated hemoglobin. Artif Cells, Blood Substitutes, Immobil. Biotech. 22: 487–501, 1994.

    Article  CAS  Google Scholar 

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Authors
  1. Ronald J. Rohlfs Ph.D
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  2. Kim D. Vandegriff Ph.D
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Editors and Affiliations

  1. School of Medicine, University of California, San Diego, CA, 92161, USA

    Robert M. Winslow M.D.  & Kim D. Vandegriff Ph.D.  & 

  2. Department of Bioengineering, University of California, San Diego, CA, 92161, USA

    Marcos Intaglietta Ph.D.

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© 1996 Birkhäuser Boston

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Rohlfs, R.J., Vandegriff, K.D. (1996). Non-phospholipid Liposomes: A Novel Method for the Preparation of Hemoglobin Containing Lipid Vesicles. In: Winslow, R.M., Vandegriff, K.D., Intaglietta, M. (eds) Blood Substitutes. Birkhäuser Boston. https://doi.org/10.1007/978-1-4612-4114-0_11

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  • DOI: https://doi.org/10.1007/978-1-4612-4114-0_11

  • Publisher Name: Birkhäuser Boston

  • Print ISBN: 978-1-4612-8659-2

  • Online ISBN: 978-1-4612-4114-0

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