Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Sep;75(9):4194–4198. doi: 10.1073/pnas.75.9.4194

Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation.

F Szoka Jr, D Papahadjopoulos
PMCID: PMC336078  PMID: 279908

Abstract

Large unilamellar and oligolamellar vesicles are formed when an aqueous buffer is introduced into a mixture of phospholipid and organic solvent and the organic solvent is subsequently removed by evaporation under reduced pressure. These vesicles can be made from various lipids or mixtures of lipids and have aqueous volume to lipid ratios that are 30 times higher than sonicated preparations and 4 times higher than multilamellar vesicles. Most importantly, a substantial fraction of the aqueous phase (up to 62% at low salt concentrations) is entrapped within the vesicles, encapsulating even large macromolecular assemblies with high efficiency. Thus, this relatively simple technique has unique advantages for encapsulating valuable water-soluble materials such as drugs, proteins, nucleic acids, and other biochemical reagents. The preparation and properties of the vesicles are described in detail.

Full text

PDF

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bangham A. D., Standish M. M., Watkins J. C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965 Aug;13(1):238–252. doi: 10.1016/s0022-2836(65)80093-6. [DOI] [PubMed] [Google Scholar]
  2. Batzri S., Korn E. D. Single bilayer liposomes prepared without sonication. Biochim Biophys Acta. 1973 Apr 16;298(4):1015–1019. doi: 10.1016/0005-2736(73)90408-2. [DOI] [PubMed] [Google Scholar]
  3. Chowhan Z. U., Yotsuyanagi T., Higuchi W. I. Model transport studies utilizing lecithin spherules. I. Critical evaluations of several physical models in the determination of the permeability coefficient for glucose. Biochim Biophys Acta. 1972 May 9;266(2):320–342. doi: 10.1016/0005-2736(72)90091-0. [DOI] [PubMed] [Google Scholar]
  4. Day E. P., Ho J. T., Kunze R. K., Jr, Sun S. T. Dynamic light scattering study of calcium-induced fusion in phospholipid vesicles. Biochim Biophys Acta. 1977 Nov 1;470(3):503–508. doi: 10.1016/0005-2736(77)90142-0. [DOI] [PubMed] [Google Scholar]
  5. Deamer D. W. Preparation and properties of ether-injection liposomes. Ann N Y Acad Sci. 1978;308:250–258. doi: 10.1111/j.1749-6632.1978.tb22027.x. [DOI] [PubMed] [Google Scholar]
  6. Deamer D., Bangham A. D. Large volume liposomes by an ether vaporization method. Biochim Biophys Acta. 1976 Sep 7;443(3):629–634. doi: 10.1016/0005-2736(76)90483-1. [DOI] [PubMed] [Google Scholar]
  7. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Liposomes and their uses in biology and medicine. Ann N Y Acad Sci. 1978;308:1–462. [PubMed] [Google Scholar]
  9. Mayhew E., Papahadjopoulos D., O'Malley J. A., Carter W. A., Vail W. J. Cellular uptake and protection against virus infection by polyinosinic-polycytidylic acid entrapped within phospholipid vesicles. Mol Pharmacol. 1977 May;13(3):488–495. [PubMed] [Google Scholar]
  10. Mayhew E., Papahadjopoulos D., Rustum Y. M., Dave C. Inhibition of tumor cell growth in vitro and in vivo by 1-beta-D-arabinofuranosylcytosine entrapped within phospholipid vesicles. Cancer Res. 1976 Dec;36(12):4406–4411. [PubMed] [Google Scholar]
  11. Ostro M. J., Giacomoni D., Dray S. Incorporation of high molecular weight RNA into large artificial lipid vesicles. Biochem Biophys Res Commun. 1977 Jun 6;76(3):836–842. doi: 10.1016/0006-291x(77)91576-5. [DOI] [PubMed] [Google Scholar]
  12. Papahadjopoulos D., Jacobson K., Nir S., Isac T. Phase transitions in phospholipid vesicles. Fluorescence polarization and permeability measurements concerning the effect of temperature and cholesterol. Biochim Biophys Acta. 1973 Jul 6;311(3):330–348. doi: 10.1016/0005-2736(73)90314-3. [DOI] [PubMed] [Google Scholar]
  13. Papahadjopoulos D., Miller N. Phospholipid model membranes. I. Structural characteristics of hydrated liquid crystals. Biochim Biophys Acta. 1967 Sep 9;135(4):624–638. doi: 10.1016/0005-2736(67)90094-6. [DOI] [PubMed] [Google Scholar]
  14. Papahadjopoulos D., Poste G., Schaeffer B. E., Vail W. J. Membrane fusion and molecular segregation in phospholipid vesicles. Biochim Biophys Acta. 1974 May 30;352(1):10–28. doi: 10.1016/0005-2736(74)90175-8. [DOI] [PubMed] [Google Scholar]
  15. Papahadjopoulos D., Vail W. J., Jacobson K., Poste G. Cochleate lipid cylinders: formation by fusion of unilamellar lipid vesicles. Biochim Biophys Acta. 1975 Jul 3;394(3):483–491. doi: 10.1016/0005-2736(75)90299-0. [DOI] [PubMed] [Google Scholar]
  16. Papahadjopoulos D., Watkins J. C. Phospholipid model membranes. II. Permeability properties of hydrated liquid crystals. Biochim Biophys Acta. 1967 Sep 9;135(4):639–652. doi: 10.1016/0005-2736(67)90095-8. [DOI] [PubMed] [Google Scholar]
  17. Ray T. K. A modified method for the isolation of the plasma membrane from rat liver. Biochim Biophys Acta. 1970 Jan 6;196(1):1–9. doi: 10.1016/0005-2736(70)90159-8. [DOI] [PubMed] [Google Scholar]
  18. Razin S. Reconstruction of biological membranes. Biochim Biophys Acta. 1972 Apr 18;265(2):241–296. [PubMed] [Google Scholar]
  19. Reeves J. P., Dowben R. M. Formation and properties of thin-walled phospholipid vesicles. J Cell Physiol. 1969 Feb;73(1):49–60. doi: 10.1002/jcp.1040730108. [DOI] [PubMed] [Google Scholar]
  20. Straub S. X., Garry R. F., Magee W. E. Interferon induction by poly (I): poly (C) enclosed in phospholipid particles. Infect Immun. 1974 Oct;10(4):783–792. doi: 10.1128/iai.10.4.783-792.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Träuble H., Grell E. Carriers and specificity in membranes. IV. Model vesicles and membranes. The formation of asymmetrical spherical lecithin vesicles. Neurosci Res Program Bull. 1971 Jun;9(3):373–380. [PubMed] [Google Scholar]
  22. Wilson T., Papahadjopoulos D., Taber R. Biological properties of poliovirus encapsulated in lipid vesicles: antibody resistance and infectivity in virus-resistant cells. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3471–3475. doi: 10.1073/pnas.74.8.3471. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES