Selective protein interactions with phosphatidylserine containing liposomes alter the steric stabilization properties of poly(ethylene glycol)

Incorporation of 5 mol%, poly(ethylene glycol)-conjugated lipids (PEG-lipid s) has been shown to extend the circulation longevity of neutral liposomes due to steric repulsion of PEG at the membrane surface. The effects of PEG- lipids on protein interactions with biologically reactive membranes were ex amined using phosphatidylserine (PS) containing liposomes as the model. Inc orporating 15 mol% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-P EG 2000 into PS liposomes resulted in circulation lifetimes comparable to t hat obtained with neutral liposomes containing 5 mol% DSPE-PEG 2000. These results suggested that 15 mol% DSPE-PEG 2000 may be effective in protecting PS liposomes from the high affinity, PS-mediated binding of plasma protein s. This was determined by monitoring the effects of PEG-lipids on calcium-m ediated blood coagulation protein interactions with PS liposomes. Prothromb in binding and procoagulant activity of PS liposomes could be inhibited > 8 0% when 15 mol% DSPE-PEG 2000 was used. These results are consistent with P S on membrane surfaces forming transient nucleation sites for protein bindi ng that may result in lateral exclusion of PEG-lipids incorporated at < 10 mol%. These nucleation sites may be inaccessible when PEG-lipids are presen t at elevated levels where they adopt a highly compressed brush conformatio n. This suggests that liposomes with reactive groups and PEG-lipids may be appropriately designed to impart selectivity to protein interactions with m embrane surfaces. (C) 2001 Elsevier Science B.V. All rights reserved.