Poly(ethylene glycol)-conjugated Phospholipids in Aqueous Micellar Solutions: Hydration, Static Structure, and Interparticle Interactions

Abstract

By means of dielec. relaxation spectroscopy (DRS) and small-angle X-ray scattering (SAXS), we have investigated hydration behavior, solvent dynamics, and static structures of aq. solns. of poly(ethylene glycol)-conjugated distearoyl phosphatidylethanolamine (DSPE-PEG) (mol. wt. of PEG: MPEG = 2000, 5000, and 12 000 Da). A quant. anal. of the bulk-water relaxation amplitude revealed the effective hydration no. of a DSPE-PEG mol. per ethylene oxide monomer unit to be ∼5.0-5.5, virtually independent of MPEG. The overall hydration no. of a DSPE-PEG mol. is ca. 20% higher than that of the corresponding normal PEG (without DSPE). This is attributed to both hydration of a charged head group of phosphoric acid in DSPE and a packing effect of PEG chains into micellar structures. The pair-distance distribution functions, p(r), extd. from the GIFT anal. of SAXS intensities show that the DSPE-PEGs form spherical-like micelles in water having the max. diam. of ∼16, 22, and 31 nm, resp., for MPEG = 2000, 5000, and 12 000 Da and nearly identical aggregation nos. of 72 (±10%). The DSPE-PEG micelles behave as charged colloids whose interparticle interaction potential can be approximated by the screened Coulomb potential model. The extd. pair correlation function g(r) demonstrates that both electrostatic repulsion induced by the charged head group and excluded vol. effects of the fully hydrated PEG layer contribute to repulsive interactions among the PEG-lipid micelles. This should be a key factor for the function of PEG lipids as a stabilizer of liposomes.