Detailed Structure of Hairy Mixed Micelles Formed by Phosphatidylcholine and PEGylated Phospholipids in Aqueous Media

Abstract

Aqueous dispersions of mixed egg yolk phosphatidylcholine (PC) and poly(ethylene glycol) (PEG) modified distearoyl phosphatidylethanolamine (DSPE) were investigated with the purpose of determining shape, size, and conformation of the formed mixed micelles. The samples were prepared at a range of DSPEPEG to PC molar ratios ([DSPEPEG/PC] from 100:0 to 30:70) and with, respectively, DSPEPEG2000 and DSPEPEG5000, where 2000 and 5000 refer to the molar masses of the PEG chains. Particle shape and internal structure were studied using small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS). The contrast of the micelles is different for X-rays and neutrons, and by combining SANS and SAXS, complementary information about the micelle structure was obtained. The detailed structure of the micelles was determined in a self-consistent way by fitting a model for the micelles to SANS and SAXS data simultaneously. In general, a model for the micelles with a hydrophobic core, surrounded by a dense hydrophilic layer that is again surrounded by a corona of PEG chains in the form of Gaussian random coils attached to the outer surface, is in good agreement with the scattering data. At high DSPEPEG contents, nearly spherical micelles are formed. As the PC content increases the micelles elongate, and at a DSPEPEG/PC ratio of 30:70, rodlike micelles longer than 1000 angstroms are formed. We demonstrate that by mixing DSPEPEG and PC a considerable latitude in controlling the particle shape is obtained. Our results indicate that the PEG chains in the corona are in a relatively unperturbed Gaussian random coil conformation even though the chains are far above the coil-coil overlap concentration and, therefore, interpenetrating. This observation in combination with the observed growth behavior questions that the "mushroom-brush"transition is the single dominating factor for determining the particle shape as assumed in previous theoretical work (Hristova, K.; Needham, D. Macromolecules 1995, 28, 991-1002).

Stability Influences the Biodistribution, Toxicity, and Anti-tumor Activity of Doxorubicin Encapsulated in PEG-PE Micelles in Mice

“…1d-f). Rod or worm-like micelles formed from the increasing ratio of phospholipid in PEGylated phospholipid have been demonstrated by the works of Hristoval et al (15) and Ashok et al (16,17), which are in agreement with our observations.…”

Controlling Lipid Micelle Stability Using Oligonucleotide Headgroups

“…Based on the size similarity to DSPE-PEG, we estimate that the particles are composed of ~90 molecules each. 20 Using small angle X-ray scattering (SAXS), we confirmed this estimation (Supplemental Table S1). SAXS data were fit to a scattering form factor for micelles with an ellipsoidal core with Gaussian chains on the surface (Figure 2B).…”

Dynamic and structural aspects of PEGylated liposomes monitored by NMR

“…Hence, it is important to evaluate the extent of PEG-lipid micellization in the formulations at their final state of concentration, pH and osmolality. A number of different methods have been employed to study PEG-lipid incorporation in liposomes including differential scanning calorimetry combined with dynamic light scattering [16,21], X-ray [22], electron spin resonance [14,15], amongst others. These methods require high concentration of the samples or the inclusion of probes in the system.…”