Biologically Active Ligand-Bearing Polymer-Grafted Liposomes

  • Samuel Zalipsky
  • Joshua Gittelman
  • Nasreen Mullah
  • Masoud M. Qazen
  • Jennifer A. Harding
Part of the NATO ASI Series book series (NSSA, volume 300)


Introduction of polymer-grafted lipid vesicles allowed to overcome some of the shortcomings of classical liposomes pertaining to their use in drug delivery, e.g. short circulating lifetimes in vivo with concomitant uptake by liver and spleen (Woodle, 1997). Optimal formulations of polymer-grafted liposomes contain 3–7 mole % of methoxypolyethylene glycol (MW 2000)-distearoylphosphatiyl-ethanolamine (mPEG-DSPE) in addition to various amounts of lecithin and cholesterol (Lasic and Martin, 1995).


Liposomal Bilayer Stealth Liposome Methoxypolyethylene Glycol Preform Liposome Antitumor Therapeutic Efficacy 
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  1. Allen, T.M., Brandeis, E., Hansen, C.B., Kao, G.Y., and Zalipsky, S., 1995, A new strategy for attachment of antibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells, Biochim. Biophys. Acta 1237:99.PubMedCrossRefGoogle Scholar
  2. Blume, G., and Cevc, G., 1993, Molecular mechanism of the lipid vesicle longevity in vivo, Biochim. Biophys. Acta 1146:157.PubMedCrossRefGoogle Scholar
  3. Blume, G., Cevc, G., Crommelin, M.D.J.A., Bakker-Woudenberg, I.A.J.M., Kluft, C, and Storm, G., 1993, 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 1149:180.PubMedCrossRefGoogle Scholar
  4. DeFrees, S.A., Phillips, L., Guo, L., and Zalipsky, S., 1996, Dramatically increased binding to E-selectin of liposomal preparation of Sialyl-Lewisx-polyethylene glycol-distearoylphosphatidylethanolamine conjugate, J. Am. Chem. Soc. 118:6101.CrossRefGoogle Scholar
  5. Gabizon, A., Catane, R., Uziely, B., Kaufman, B., Safra, T., Cohen, R., Martin, F., Huang, A., and Barenholz, Y., 1994, Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene glycol coated liposomes, Cancer. Res. 54:987.PubMedGoogle Scholar
  6. Goren, D., Horowitz, A.T., Zalipsky, S., Woodle, M.C., Yarden, Y., and Gabizon, A., 1996, Targeting of Stealth liposomes to erbB2 (Her/2) receptor: In vitro and in vivo studies, Br. J. Cancer 74:1749.PubMedCrossRefGoogle Scholar
  7. Goren, D., Horowitz, A.T., Mandelbaum-Shavit, F., Tzemach, D., Zalipsky, S., and Gabizon, A., 1997, In vitro and in vivo studies of folate-targeted liposomes, Proc.Int.Symp. Control. Rel. Bioact. Mater. 24:865.Google Scholar
  8. Hansen, C.B., Kao, G.Y., Moase, E.H., Zalipsky, S., and Allen, T.M., 1995, Attachment of antibodies to sterically stabilized liposomes: Evaluation, comparison and optimization of coupling procedures, Biochim. Biophys. Acta 1239:133.PubMedCrossRefGoogle Scholar
  9. Harding, J.A., Engbers, CM., Newman, M.S., Goldstein, N.I., and Zalipsky, S., 1997, Immunogenicity and pharmacokinetic attributes of poly(ethylene glycol)-grafted immunoliposomes, Biochim. Biophys. Acta 1327:181.PubMedCrossRefGoogle Scholar
  10. Harris, J.M., and Zalipsky, S. 1997, Poly(ethylene glycol): Chemistry and Biological Applications, ACS Symposium series 680, Washington.CrossRefGoogle Scholar
  11. Kirpotin, D., Park, J.W., Hong, K., Zalipsky, S., Li, W.-L., Carter, P., Benz, C.C., and Papahadjopoulos, D., 1996, Sterically stabilized anti-Her2 immunoliposomes: Design and targeting to human breast cancer cells in vitro, Biochemistry 36:66.CrossRefGoogle Scholar
  12. Klibanov, A.L., Maruyama, K., Beckerleg, A.M., Torchilin, V.P., and Huang, L., 1991, Activity of amphiphathic 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 1062:142.PubMedCrossRefGoogle Scholar
  13. Lasic, D.D., and Martin, F., 1995, eds., Stealth Liposomes, CRC Press, Boca Raton.Google Scholar
  14. Lee, R.J., and Low, P.S., 1994, Delivery of liposomes into cultured KB cells via folate receptor-mediated endocytosis, J. Biol. Chem. 269:3198.PubMedGoogle Scholar
  15. 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, and Martin, F.J., 1991, Sterically stabilized liposomes: Improvements in pharmacokinetics and antitumor therapeutic efficacy, Proc.Natl Acad Sci. USA, 88:11460.PubMedCrossRefGoogle Scholar
  16. Phillips, N.C., Gagne, L., Tsoukas, C., and Dahman, J., 1994, Immunoliposome targeting to murine CD4+ leucocytes is dependent on immune status, J. Immunol. 152:3168.PubMedGoogle Scholar
  17. Sato, T., and Sunamoto, J., 1992, Recent aspects in the use of liposomes in biotechnology and medicine, Prog. Lipid Res. 31:345.PubMedCrossRefGoogle Scholar
  18. Shimada, K., Kamps, J.A.A.M., Regts, J., Ikeda, K., Shiozawa, T., Hirota, S., and Scherphof, G.L., 1997, Bio-distribution of liposomes containing synthetic galactose-terminated diacylglycerol-poly(ethylene glycol)s, Biochim. Biophys. Acta 1326:329.PubMedCrossRefGoogle Scholar
  19. Silvius, J.R., and Zuckermann, M.J., 1993, Interbilayer transfer of phospholipid-anchored macromolecules via monomer diffusion, Biochemistry 32:3153.PubMedCrossRefGoogle Scholar
  20. Torchilin, V.P., and Papisov, M.I., 1994, Why do polyethylene glycol-coated liposomes circulate so long?, J. Liposome Res. 4:725.CrossRefGoogle Scholar
  21. Uster, P.S., Allen, T.M., Daniels, B.E., Mendez, C.J., Newman, M.S., and Zhu, G.Z., 1996, Insertion of poly(ethylene glycol) derivatized phospholipid into pre-formed liposomes results in prolonged in vivo circulation time, FEBS Lett. 386:243.PubMedCrossRefGoogle Scholar
  22. Wong, J., Kuhl, T.L., Israelashvili, J.N., Mullah, N., and Zalipsky, S., 1996, Direct measurement of tethered ligand-receptor interaction potential, Science 275:820.CrossRefGoogle Scholar
  23. Woodle, M.C., 1997, PEG-grafted liposome therapeutics, in: Poly(ethylene glycol): Chemistry and Biological Applications, J.M. Harris and S. Zalipsky, eds., ACS Symposium series 680, Washington.Google Scholar
  24. Woodle, M.C., and Lasic, D.D., 1992, Sterically stabilized liposomes, Biochim. Biophys. Acta, 1113:171.PubMedCrossRefGoogle Scholar
  25. Woodle, M.C., Engbers, CM., and Zalipsky, S., 1994, New amphipathic polymer-lipid conjugates forming long-circulating reticuloendothelial system-evading liposomes, Bioconjugate Chem. 5:493.CrossRefGoogle Scholar
  26. Zalipsky, S., 1993, Synthesis of end-group functionalized polyethylene glycol-lipid conjugate for preparation of polymer-grafted liposomes, Bioconjugate Chem. 4:296.CrossRefGoogle Scholar
  27. Zalipsky, S., 1995a, PEG-lipid conjugates, in: Stealth Liposomes, Lasic, D. and Martin, F., eds., CRC Press, Boca Raton.Google Scholar
  28. Zalipsky, S., 1995b, Functionalized poly(ethylene glycol) for preparation of biologically relevant conjugates, Bioconjugate Chem. 6:150.CrossRefGoogle Scholar
  29. Zalipsky, S., and Barany, G., 1986, Preparation of polyethylene glycol derivatives with two different groups at the termini, Polym. Prepr. Am. Chem. Soc. Div. Polym. Chem. 27:1.Google Scholar
  30. Zalipsky, S., and Barany, G., 1990, Facile synthesis of α-hydroxy-ω)-carboxymethyl-polyethylene oxide, J. Bioact. Compatible Polym. 5:227.CrossRefGoogle Scholar
  31. Zalipsky, S., Chang, J.L., Albericio, F., and Barany, G., 1994a, Preparation and applications of polyethylene glycol-polystyrene graft resin supports for solid-phase peptide synthesis, Reactive Polym. 22:243.CrossRefGoogle Scholar
  32. Zalipsky, S., Brandeis, E., Newman, M.S., and Woodle, M.C., 1994b, Long-circulating, cationic liposomes containing amino-PEG-phosphatidylethanolamine, FEBS Lett. 353:71.PubMedCrossRefGoogle Scholar
  33. Zalipsky, S., Puntambekar, B., Bolikas, P., Engbers, CM., and Woodle, M.C., 1995, Peptide attachment to extremities of liposomal surface grafted PEG chains: Preparation of the long-circulating form of laminin pentapeptide, YIGSR, Bioconjugate Chem., 6:705.CrossRefGoogle Scholar
  34. Zalipsky, S., Hansen, C.B., Lopes de Menezes, D.E., and Allen, T.M., 1996, Long-circulating, polyethylene glycol-grafted immunoliposomes, J. Controlled Release 39:153.CrossRefGoogle Scholar
  35. Zalipsky, S., Mullah, N., Harding, J.A., Gittelman, J., Guo, L., and DeFrees, S.A., 1997, Poly(ethylene glycol)-grafted liposomes with oligosaccharide or oligopeptide ligands appended to the tethered termini of the polymer chains, Bioconjugate Chem. 8:111.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Samuel Zalipsky
    • 1
  • Joshua Gittelman
    • 1
  • Nasreen Mullah
    • 1
  • Masoud M. Qazen
    • 1
  • Jennifer A. Harding
    • 1
  1. 1.SEQUUS Pharmaceuticals, Inc.Menlo ParkUSA

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