Simulations Study of Single-Component and Mixed n-Alkyl-PEG Micelles

Abstract

Here, we study one-component and mixed n-alkyl-poly(ethylene glycol) (CmEn) micelles with varying poly(ethylene glycol) (PEG) chain lengths n using coarse-grained molecular simulations. These nonionic alkyl-PEG surfactants and their aggregates are widely used in bio and chemical technology. As expected, the simulations show that increasing the PEG chain length decreases the alkyl-PEG micelle core diameter and the aggregation number but also enhances PEG chain penetration to the core region and spreads the micelle corona. Both the core and corona density are heavily dependent on the PEG chain length and decrease with increasing PEG length. Furthermore, we find that the alkyl-PEG surfactants exhibit two distinct micellization modes: surfactants with short PEG chains as their hydrophilic heads aggregate with the PEG heads relatively extended. Their aggregation number and the PEG corona density are dictated by the core carbon density. For longer PEG chains, the PEG sterics, that is, the volume occupied by the PEG head group, becomes the critical factor limiting the aggregation. Finally, simulations of binary mixtures of alkyl-PEGs of two different PEG chain lengths show that even in the absence of core-freezing, the surfactants prefer the aggregate size of their single-component solutions with the segregation propelled via enthalpic contributions. The findings, especially as they provide a handle on the density and the density profile of the aggregates, raise attention to effective packing shape as a design factor of micellar systems, for example, drug transport, solubilization, or partitioning.

Molecular Simulations of PEGylated Biomolecules, Liposomes, and Nanoparticles for Drug Delivery Applications

“…It is worth noting that the binding between plasma protein and bilayer surface can be predicted from the boundary between mushroom and brush states of PEG with different sizes and grafting densities, as highlighted in Figure 7 . Recently, Sammalkorpi and coworkers showed the formation of self-assembled liposomes, bicelles, and micelles at different PEGylated-lipid concentrations [ 169 , 170 ], similar to our previous work [ 167 ].…”

Spherical Micelles with Nonspherical Cores: Effect of Chain Packing on the Micellar Shape

“…They also found a slight anisotropy which might become more pronounced with longer n -alkyl chains. 18 In addition, the persistent core anisotropy in the liquidlike phase can be explained by dynamic fluctuations of the core. As these fluctuations occur on time scales much shorter than the temporal resolution of the scattering experiment, only an averaged ellipsoidal shape is observable.…”

Tale of Two Tails: Molecular Exchange Kinetics of Telechelic Polymer Micelles

“…At least computer simulations of C 18 -PEOx only revealed a slight anisotropy. [103] During the structural analysis of mixed C n -PEO5 micelles we discovered an unpredicted N agg ∝ n 3 scaling law (Paper II). As we to this date lack an explanation, more experimental and theoretical work is mandatory to confirm or reject this finding.…”

“…Commercially, a number of C n -PEOx derivatives are available under the trade name "Brij" and have found several applications, among others in the pharmaceutical sector. [91][92][93][94][95][96] Due to its archetypical features, C n -PEOx has been extensively employed to study micellar aggregation [97][98][99][100][101][102][103] and rheological response [40,104]. Furthermore, it has proven to be particularly suited to study the molecular exchange kinetics between polymeric micelles  see Section 1.5.2 on page 15.…”

“…[261] Also the coarse-grained molecular simulations of Vuorte et al revealed a slight anisotropy in amorphous C 18 -PEOx micellar cores, which might become more pronounced with longer alkyl chains. [103] On the other hand, core crystallization does not always lead to an anisotropic shape. For example, Sevgen et al reported atomistic simulations of oligo(ethylene sulfide)-poly(ethylene glycol) (OES-PEG) micelles which maintained their spherical shape, despite partial crystallization of the OES blocks.…”