Molecular Modeling of Complex Cross-Linked Networks of PEGDA Nanogels

Poly(ethylene glycol) (PEG)-based nanogels are attractive for biomedical applications due to their biocompatibility, versatile end group chemistry, and ability to sterically shield encapsulated drug molecules. The characteristics of a hydrogel network govern the encapsulation and efficient delivery of drug molecules for a target application. A molecular-level description of network topology can complement experimental investigations to understand its effects on the structural properties of these nanogels. In this work, atomistic molecular simulations of heterogeneous, nonideal PEG-diacrylate (PEGDA) nanogels are presented. The effects of cross-linking density and topological features on the structural properties of PEGDA nanogels were studied. The average functionality was controlled to systematically study the effect of cross-linking density on the radius of gyration, shape, and mesh size of the nanogels. For a given average functionality, the impact of distinct network topologies on the structural properties was also studied. The aspect ratios, based on the gyration tensor, were calculated to characterize the shapes of these nanogels for different topologies. Nanogel structures with higher cross-linking densities showed a globular shape, while structures with lower cross-linking density showed shape anisotropy. The distribution and connectivity of the cross-linked junctions played a key role in determining the size and shape anisotropy of PEGDA nanogels; the number of unreacted chain ends and their connectivity directly affected the anisotropy. The mesh size, denoted by the limiting "free volume element" present in the nanogel samples, does not show a significant change with increasing average functionality. This work provides insight into the structural properties of heterogeneous hydrogels that aid the design of nonideal nanogel networks for a targeted drug delivery application.