Association of hydrophobically-modified poly(ethylene glycol) with fusogenic liposomes

Debra T. Auguste, Robert K. Prud'homme, Patrick L. Ahl, Paul Meers, Joachim Kohn

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

We present results on using cooperative interactions to shield liposomes by incorporating multiple hydrophobic anchoring sites on polyethylene glycol (PEG) polymers. The hydrophobically-modified PEGs (HMPEGs) are comb-graft polymers with strictly alternating monodisperse PEG blocks (Mw=6, 12, or 35 kDa) bonded to C18 stearylamide hydrophobes. Cooperativity is varied by changing the degree of oligomerization at a constant ratio of PEG to stearylamide. Fusogenic liposomes prepared from N-C12-DOPE:DOPC 7:3 (mol:mol) were equilibrated with HMPEGs. Affinity for polymer association to liposomes increases with the degree of oligomerization; equilibrium constants (given as surface coverage per equilibrium concentration of free polymer) for 6 kDa PEG increased from 6.1±0.8 (mg/m2)/(mg/ml) for 2.5 loops to 78.1±12.2 (mg/m2)/(mg/ml) for 13 loops. In contrast, the equilibrium constant for distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG5k) was 0.4±0.1 (mg/m2)/(mg/ml). The multi-loop HMPEGs demonstrate higher levels of protection from complement binding than DSPE-PEG5k. Greater protection does not correlate with binding strength alone. The best shielding was by HMPEG6k-DP3 (with three 6 kDa PEG loops), suggesting that PEG chains with adequate surface mobility provide optimal protection from complement opsonization. Complement binding at 30 min and 12 h demonstrates that protection by multi-looped PEGs is constant whereas DSPE-PEG5k initially protects but presumably partitions off of the surface at longer times.

Original languageEnglish (US)
Pages (from-to)184-195
Number of pages12
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1616
Issue number2
DOIs
StatePublished - Oct 13 2003

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Cell Biology

Keywords

  • Comb-graft
  • Complement assay
  • Fusogenic liposome
  • Hydrophobically modified PEG
  • Liposome protection
  • Protein shielding

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