Polymer-grafted liposomes: Physical basis for the "stealth" property

D. Needham, K. Hristova, T. J. Mcintosh, M. Dewhirst, N. Wu, D. D. Lasic

Research output: Contribution to journalArticlepeer-review


Polymer-bearing lipids have recently been incorporated into liposomes that are used in in vivo drug delivery. This strategy has improved the liposome's ability to avoid the reticuloendothelial system and has thereby increased its circulation time in the bloodstream. In order to understand the physical basis for this, so called, Stealth® effect, we have begun a series of studies that characterize the surface structure, interactive properties and in vivo performance of the polymer-bearing, Stealth lipids. For a 1900 g/mol polyethylene glycol (PEG) moiety, we have used x-ray diffraction and micropipet manipulation methods to show that, (i) the polymer chains extend ∼50Å out from the lipid bilayer surface; (ii) this surface polymer exerts a significant long range mutual repulsion between adjacent bilayers that prevents bilayer-bilayer adhesion. Furthermore, the measured polymer extension and repulsive pressure are well modelled by polymer scaling laws. These results imply that the interaction of macromolecules and cellular surfaces with the Stealth liposome is probably limited to a distance of ∼50Å from the liposome surface. We conclude that the origin of the Stealth effect lies in a steric stabilization mechanism. By using fluorescence video microscopy to observe implanted tumor tissue, we have also shown that fluorescent Stealth liposomes extravasate through the leaky vessel walls of tumors. This method allows us to characterize, in real time, the accumulation of liposomes and release of drug at an implanted tumor site.

Original languageEnglish (US)
Pages (from-to)411-430
Number of pages20
JournalJournal of Liposome Research
Issue number3
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Pharmaceutical Science


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