We have performed all atom explicit solvent molecular dynamics simulations of three different star polymeric systems in water, each star molecule consisting of 16 diblock copolymer arms bound to a small adamantane core. The arms of each system consist of an inner "hydrophobic" block (either polylactide, polyvalerolactone, or polyethylene) and an outer hydrophilic block (polyethylene oxide, PEO). These models exhibit unusual structure very close to the core (clearly an artifact of our model) but which we believe becomes "normal" or bulk-like at relatively short distances from this core. We report on a number of temperature-dependent thermodynamic (structural/energetic) properties as well as kinetic properties. Our observations suggest that under physiological conditions, the hydrophobic regions of these systems may be solid and glassy, with only rare and shallow penetration by water, and that a sharp boundary exists between the hydrophobic cores and either the PEO or water. The PEO in these models is seen to be fully water-solvated at low temperatures but tends to phase separate from water as the temperature is increased, reminiscent of a lower critical solution temperature exhibited by PEO-water mixtures. Water penetration concentration and depth is composition and temperature dependent with greater water penetration for the most ester-rich star polymer.

We present a molecular dynamics study of the effect of core chemistry on star polymer structural and kinetic properties. This work serves to validate the choice of a model adamantane core used in previous simulations to represent larger star polymeric systems in an aqueous environment, as well as to explore how the choice of size and core chemistry using a dendrimer or nanogel core may affect these polymeric nanoparticle systems, particularly with respect to thermosensitivity and solvation properties that are relevant for applications in drug loading and delivery.

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To develop a detailed picture of the microscopic structure of gelcore star polymers and to elucidate parameters of the synthetic process that might be exploited to control this structure, simulations of their synthesis were performed that were based on a particular synthetic approach. A range of results was observed from gelation at high reactant concentrations to the formation of various sizes and compositions of star polymers. Contrary to the prevailing experimental viewpoint, the simulations always suggest the production of a broad distribution of star polymer sizes. However, the GPC traces computed from simulation results are in good qualitative agreement with experiment. Topologically, the gelcore star polymers produced by simulation are not compact but, rather, sparse blobs loosely connected by filaments of linker when modeled in a good solvent. This is reflected in scaling relationships that relate polymer size (e.g., radius of gyration) and degree of polymerization. The arm-core composition is observed to be stoichiometric, strongly reflecting relative reactant concentrations during the synthesis. Reactions within star polymers that result in greater intramolecular cross-linking compete with those between star polymers that result in the production of larger star polymers from the joining of smaller ones. The balance in this competition can be controlled through the overall reactant concentration to limit and control resulting star polymer size. Therefore, the mean size, as well as the mean number of arms, can be controlled during synthesis by careful tuning of the overall ratio of the arm and linker reactant concentrations and the total reactant concentration.

Star polymers with a cross-linked nanogel core are promising carriers of cargo for therapeutic applications due to the synthetic control of amphiphilicity of arms and stability at infinite dilution. Three nanogel-core star polymers were investigated to understand how the arm-block chemical structure controls loading efficiency of a model drug, ibuprofen, and its spatial distribution. The spatial distribution profiles of hydrophobic core, hydrophilic corona, and encapsulated drug were determined by small-angle neutron scattering (SANS). SANS provides the nanometer-scale sensitivity to determine how the arm-block chemistry enhances the sequestering of ibuprofen. Validated molecular dynamics simulations capture the trends in drug profile and polymer segment distribution with further details on drug orientation distribution. This work provides a basis to study structure-function relationships in macromolecular-based carriers of cargo and represents a path toward validated and predictive simulation.