Polymer vesicles in vivo: Correlations with PEG molecular weight

Peter J. Photos, Lucie Bacakova, Bohdana Discher, Frank S. Bates, Dennis E. Discher

Research output: Contribution to journalArticlepeer-review

417 Scopus citations

Abstract

PEG-modified lipid vesicles have already shown considerable utility in delaying vesicle clearance from the circulation. They are, however, limited in their ability to stably integrate high molar ratios of PEG-lipid due to the high curvature and micellar preference of the very large hydrophilic PEG chain. Polymersomes, by contrast, are vesicles composed entirely of PEG-based block copolymer amphiphiles that are not only more proportionately designed, but also have already been shown to considerably broaden the range of vesicle properties (e.g. stability). Here, polymersomes composed of varying length copolymer chains were injected into rats and found to have in vivo circulation times, τ1/2, up to about two-fold longer than PEGylated, or Stealth, liposomes. The dependence of τ1/2 on PEG molecular weight is nonetheless limited by uptake into the liver and spleen - as with liposomes. In vitro incubations of polymersomes in plasma indicate gradual opsonization through plasma protein adsorption, such that, when vesicles are held in an optical trap and presented to a phagocyte, rapid engulfment occurs only after incubation times of similar magnitude to τ1/2. The stealthiness introduced to liposomes through PEGylation is thus extended here with completely synthetic polymersomes.

Original languageEnglish (US)
Pages (from-to)323-334
Number of pages12
JournalJournal of Controlled Release
Volume90
Issue number3
DOIs
StatePublished - Jul 31 2003

Keywords

  • Circulation times
  • Long circulating
  • PEGylation
  • Polymersomes
  • Stealth liposomes

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