Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1995 May;68(5):1921–1936. doi: 10.1016/S0006-3495(95)80369-3

Range and magnitude of the steric pressure between bilayers containing phospholipids with covalently attached poly(ethylene glycol).

A K Kenworthy 1, K Hristova 1, D Needham 1, T J McIntosh 1
PMCID: PMC1282095  PMID: 7612834

Abstract

The interactive properties of liposomes containing phospholipids with covalently attached poly(ethylene glycol) (PEG-lipids) are of interest because such liposomes are being developed as drug delivery vehicles and also are ideal model systems for measuring the properties of surface-grafted polymers. For bilayers containing PEG-lipids with PEG molecular weights of 350, 750, 2000, and 5000, pressure-distance relations have been measured by X-ray diffraction analysis of liposomes subjected to known applied osmotic pressures. The distance between apposing bilayers decreased monotonically with increasing applied pressure for each concentration of a given PEG-lipid. Although for bilayers containing PEG-350 and PEG-750 the contribution of electrostatic repulsion to interbilayer interactions was significant, for bilayers containing PEG-2000 and PEG-5000 the major repulsive pressure between bilayers was a steric pressure due to the attached PEG. The range and magnitude of this steric pressure increased both with increasing PEG-lipid concentration and PEG size, and the extension length of the PEG from the bilayer surface at maximum PEG-lipid concentration depended strongly on the size of the PEG, being less than 35 A for PEG-750, and about 65 A for PEG-2000 and 115 A for PEG-5000. The measured pressure-distance relations have been modeled in terms of current theories (deGennes, 1987; Milner et al., 1988b) for the steric pressure produced by surface-grafted polymers, as modified by us to take into account the effects of polymer polydispersity and the possibility that, at low grafting densities, polymers from apposing bilayers surfaces can interpenetrate or interdigitate. No one theoretical scheme is sufficient to account for all the experimental results. However, for a given pressure regime, PEG-lipid size, and PEG-lipid surface density, the appropriately modified theoretical treatment gives a reasonable fit to the pressure-distance data.

Full text

PDF
1921

Selected References

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

  1. Allen T. M., Hansen C., Martin F., Redemann C., Yau-Young A. Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim Biophys Acta. 1991 Jul 1;1066(1):29–36. doi: 10.1016/0005-2736(91)90246-5. [DOI] [PubMed] [Google Scholar]
  2. Allen T. M., Hansen C. Pharmacokinetics of stealth versus conventional liposomes: effect of dose. Biochim Biophys Acta. 1991 Sep 30;1068(2):133–141. doi: 10.1016/0005-2736(91)90201-i. [DOI] [PubMed] [Google Scholar]
  3. Blume G., Cevc G., Crommelin M. D., Bakker-Woudenberg I. A., Kluft C., Storm G. Specific targeting with poly(ethylene glycol)-modified liposomes: coupling of homing devices to the ends of the polymeric chains combines effective target binding with long circulation times. Biochim Biophys Acta. 1993 Jun 18;1149(1):180–184. doi: 10.1016/0005-2736(93)90039-3. [DOI] [PubMed] [Google Scholar]
  4. Blume G., Cevc G. Liposomes for the sustained drug release in vivo. Biochim Biophys Acta. 1990 Nov 2;1029(1):91–97. doi: 10.1016/0005-2736(90)90440-y. [DOI] [PubMed] [Google Scholar]
  5. Cowley A. C., Fuller N. L., Rand R. P., Parsegian V. A. Measurement of repulsive forces between charged phospholipid bilayers. Biochemistry. 1978 Jul 25;17(15):3163–3168. doi: 10.1021/bi00608a034. [DOI] [PubMed] [Google Scholar]
  6. Eisenberg M., Gresalfi T., Riccio T., McLaughlin S. Adsorption of monovalent cations to bilayer membranes containing negative phospholipids. Biochemistry. 1979 Nov 13;18(23):5213–5223. doi: 10.1021/bi00590a028. [DOI] [PubMed] [Google Scholar]
  7. Evans E. A., Parsegian V. A. Thermal-mechanical fluctuations enhance repulsion between bimolecular layers. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7132–7136. doi: 10.1073/pnas.83.19.7132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gabizon A. A. Selective tumor localization and improved therapeutic index of anthracyclines encapsulated in long-circulating liposomes. Cancer Res. 1992 Feb 15;52(4):891–896. [PubMed] [Google Scholar]
  9. Kim J. T., Mattai J., Shipley G. G. Gel phase polymorphism in ether-linked dihexadecylphosphatidylcholine bilayers. Biochemistry. 1987 Oct 20;26(21):6592–6598. doi: 10.1021/bi00395a005. [DOI] [PubMed] [Google Scholar]
  10. Klibanov A. L., Maruyama K., Beckerleg A. M., Torchilin V. P., Huang L. Activity of amphipathic poly(ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding to target. Biochim Biophys Acta. 1991 Feb 25;1062(2):142–148. doi: 10.1016/0005-2736(91)90385-l. [DOI] [PubMed] [Google Scholar]
  11. Klibanov A. L., Maruyama K., Torchilin V. P., Huang L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 1990 Jul 30;268(1):235–237. doi: 10.1016/0014-5793(90)81016-h. [DOI] [PubMed] [Google Scholar]
  12. Kuhl T. L., Leckband D. E., Lasic D. D., Israelachvili J. N. Modulation of interaction forces between bilayers exposing short-chained ethylene oxide headgroups. Biophys J. 1994 May;66(5):1479–1488. doi: 10.1016/S0006-3495(94)80938-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lasic D. D., Martin F. J., Gabizon A., Huang S. K., Papahadjopoulos D. Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times. Biochim Biophys Acta. 1991 Nov 18;1070(1):187–192. doi: 10.1016/0005-2736(91)90162-2. [DOI] [PubMed] [Google Scholar]
  14. LeNeveu D. M., Rand R. P. Measurement and modification of forces between lecithin bilayers. Biophys J. 1977 May;18(2):209–230. doi: 10.1016/S0006-3495(77)85608-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mayhew E. G., Lasic D., Babbar S., Martin F. J. Pharmacokinetics and antitumor activity of epirubicin encapsulated in long-circulating liposomes incorporating a polyethylene glycol-derivatized phospholipid. Int J Cancer. 1992 May 8;51(2):302–309. doi: 10.1002/ijc.2910510221. [DOI] [PubMed] [Google Scholar]
  16. McIntosh T. J., Magid A. D., Simon S. A. Cholesterol modifies the short-range repulsive interactions between phosphatidylcholine membranes. Biochemistry. 1989 Jan 10;28(1):17–25. doi: 10.1021/bi00427a004. [DOI] [PubMed] [Google Scholar]
  17. McIntosh T. J., Magid A. D., Simon S. A. Range of the solvation pressure between lipid membranes: dependence on the packing density of solvent molecules. Biochemistry. 1989 Sep 19;28(19):7904–7912. doi: 10.1021/bi00445a053. [DOI] [PubMed] [Google Scholar]
  18. McIntosh T. J., Magid A. D., Simon S. A. Steric repulsion between phosphatidylcholine bilayers. Biochemistry. 1987 Nov 17;26(23):7325–7332. doi: 10.1021/bi00397a020. [DOI] [PubMed] [Google Scholar]
  19. McIntosh T. J., Simon S. A. Contributions of hydration and steric (entropic) pressures to the interactions between phosphatidylcholine bilayers: experiments with the subgel phase. Biochemistry. 1993 Aug 17;32(32):8374–8384. doi: 10.1021/bi00083a042. [DOI] [PubMed] [Google Scholar]
  20. McIntosh T. J., Simon S. A. Hydration force and bilayer deformation: a reevaluation. Biochemistry. 1986 Jul 15;25(14):4058–4066. doi: 10.1021/bi00362a011. [DOI] [PubMed] [Google Scholar]
  21. McIntosh T. J., Simon S. A., Needham D., Huang C. H. Interbilayer interactions between sphingomyelin and sphingomyelin/cholesterol bilayers. Biochemistry. 1992 Feb 25;31(7):2020–2024. doi: 10.1021/bi00122a018. [DOI] [PubMed] [Google Scholar]
  22. Milner S. T. Polymer brushes. Science. 1991 Feb 22;251(4996):905–914. doi: 10.1126/science.251.4996.905. [DOI] [PubMed] [Google Scholar]
  23. Mori A., Klibanov A. L., Torchilin V. P., Huang L. Influence of the steric barrier activity of amphipathic poly(ethyleneglycol) and ganglioside GM1 on the circulation time of liposomes and on the target binding of immunoliposomes in vivo. FEBS Lett. 1991 Jun 24;284(2):263–266. doi: 10.1016/0014-5793(91)80699-4. [DOI] [PubMed] [Google Scholar]
  24. Needham D., McIntosh T. J., Lasic D. D. Repulsive interactions and mechanical stability of polymer-grafted lipid membranes. Biochim Biophys Acta. 1992 Jul 8;1108(1):40–48. doi: 10.1016/0005-2736(92)90112-y. [DOI] [PubMed] [Google Scholar]
  25. Papahadjopoulos D., Allen T. M., Gabizon A., Mayhew E., Matthay K., Huang S. K., Lee K. D., Woodle M. C., Lasic D. D., Redemann C. Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11460–11464. doi: 10.1073/pnas.88.24.11460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Parsegian V. A., Fuller N., Rand R. P. Measured work of deformation and repulsion of lecithin bilayers. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2750–2754. doi: 10.1073/pnas.76.6.2750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Parsegian V. A., Rand R. P., Fuller N. L., Rau D. C. Osmotic stress for the direct measurement of intermolecular forces. Methods Enzymol. 1986;127:400–416. doi: 10.1016/0076-6879(86)27032-9. [DOI] [PubMed] [Google Scholar]
  28. Ranck J. L., Keira T., Luzzati V. A novel packing of the hydrocarbon chains in lipids. The low temperature phases of dipalmitoyl phosphatidyl-glycerol. Biochim Biophys Acta. 1977 Sep 28;488(3):432–441. doi: 10.1016/0005-2760(77)90201-6. [DOI] [PubMed] [Google Scholar]
  29. Woodle M. C., Collins L. R., Sponsler E., Kossovsky N., Papahadjopoulos D., Martin F. J. Sterically stabilized liposomes. Reduction in electrophoretic mobility but not electrostatic surface potential. Biophys J. 1992 Apr;61(4):902–910. doi: 10.1016/S0006-3495(92)81897-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Woodle M. C., Lasic D. D. Sterically stabilized liposomes. Biochim Biophys Acta. 1992 Aug 14;1113(2):171–199. doi: 10.1016/0304-4157(92)90038-c. [DOI] [PubMed] [Google Scholar]
  31. Woodle M. C., Matthay K. K., Newman M. S., Hidayat J. E., Collins L. R., Redemann C., Martin F. J., Papahadjopoulos D. Versatility in lipid compositions showing prolonged circulation with sterically stabilized liposomes. Biochim Biophys Acta. 1992 Apr 13;1105(2):193–200. doi: 10.1016/0005-2736(92)90194-q. [DOI] [PubMed] [Google Scholar]
  32. Wu N. Z., Da D., Rudoll T. L., Needham D., Whorton A. R., Dewhirst M. W. Increased microvascular permeability contributes to preferential accumulation of Stealth liposomes in tumor tissue. Cancer Res. 1993 Aug 15;53(16):3765–3770. [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES