Spin-label electron spin resonance (ESR) spectroscopy and auxiliary optical density measurements are used to study lipid dispersions of N-poly(ethylene glycol)-dipalmitoyl phosphatidylethanolamine (PEG:5000-DPPE) mixed with dipalmitoyl phosphatidylcholine (DPPC). PEG:5000-DPPE bears a large hydrophilic polymer headgroup (with approximately 114 oxyethylene monomers) and is commonly used for steric stabilization of liposomes used in drug delivery. Comparison is made with results from mixtures of DPPC with polymer lipids bearing shorter headgroups (approximately 45 and 8 oxyethylene monomers). ESR spectra of phosphatidylcholine spin-labeled on the 5-C atom position of the sn-2 chain are shown to reflect the area expansion of the lipid membranes by the lateral pressure exerted in the polymer brush, in a way that is consistent with theory. The lipid chain packing density at the onset of micelle formation is the same for all three PEG-lipids, although the mole fraction at which this occurs differs greatly. The mole fraction at onset scales inversely with the size of the polymer headgroup, where the experimental exponent of 0.7 is close to theoretical predictions (viz. 0.55-0.6). The mole fraction of PEG-lipid at completion of micelle formation is more weakly dependent on polymer size, which conforms with theoretical predictions. At high mole fractions of PEG:5000-DPPE the dependence of lipid packing density on mole fraction is multiphasic, which differs qualitatively from the monotonic decrease in packing density found with the shorter polymer lipids. Lipid spin-label ESR is an experimental tool that complements theoretical analysis using polymer models combined with the lipid equation of state.

Spin-label electron spin resonance (ESR) spectroscopy, together with optical density measurements, has been used to investigate, at both the molecular and supramolecular levels, the interactions of N-poly(ethylene glycol)-phosphatidylethanolamines (PEG-PE) with phosphatidylcholine (PC) in aqueous dispersions. PEG-PEs are micelle-forming hydrophilic polymer-grafted lipids that are used extensively for steric stabilization of PC liposomes to increase their lifetimes in the blood circulation. All lipids had dipalmitoyl (C16:0) chains, and the polymer polar group of the PEG-PE lipids had a mean molecular mass of either 350 or 2000 Da. PC/PEG-PE mixtures were investigated over the entire range of relative compositions. Spin-label ESR was used quantitatively to investigate bilayer-micelle conversion with increasing PEG-PE content by measurements at temperatures for which the bilayer membrane component of the mixture was in the gel phase. Both saturation transfer ESR and optical density measurements were used to obtain information on the dependence of lipid aggregate size on PEG-PE content. It is found that the stable state of lipid aggregation is strongly dependent not only on PEG-PE content but also on the size of the hydrophilic polar group. These biophysical properties may be used for optimized design of sterically stabilized liposomes.

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