Electrostatic hindrance to diffusion in flexible crosslinked gels: A coarse-grained simulation study.

In this work, we study how electrostatic forces slow down the diffusion of solute in flexible gels through coarse-grained simulations. The model used explicitly considers the movement of solute particles and polyelectrolyte chains. These movements are performed by following a Brownian dynamics algorithm. The effect of three electrostatic parameters characterizing the system (solute charge, polyelectrolyte chain charge, and ionic strength) is analyzed. Our results show that the behavior of both the diffusion coefficient and the anomalous diffusion exponent changes upon the reversal of the electric charge of one of the species. In addition, the diffusion coefficient in flexible gels differs significantly from that in rigid gels if the ionic strength is low enough. However, the effect of chain flexibility on the exponent of anomalous diffusion is significant even at high ionic strength (100 mM). Our simulations also prove that varying the polyelectrolyte chain charge does not have exactly the same effect as varying the solute particle charge.

Coarse-Grained Simulations of Release of Drugs Housed in Flexible Nanogels: New Insights into Kinetic Parameters.

The diffusion-controlled release of drugs housed in flexible nanogels has been simulated with the help of a coarse-grained model that explicitly considers polymer chains. In these in silico experiments, the effect of its flexibility is assessed by comparing it with data obtained for a rigid nanogel with the same volume fraction and topology. Our results show that the initial distribution of the drug can exert a great influence on the release kinetics. This work also reveals that certain surface phenomena driven by steric interactions can lead to apparently counterintuitive behaviors. Such phenomena are not usually included in many theoretical treatments used for the analysis of experimental release kinetics. Therefore, one should be very careful in drawing conclusions from these formalisms. In fact, our results suggest that the interpretation of drug release curves in terms of kinetic exponents (obtained from the Ritger-Peppas Equation) is a tricky question. However, such curves can provide a first estimate of the drug diffusion coefficient.

Coarse-grained Monte Carlo simulations of nanogel-polyelectrolyte complexes: electrostatic effects.

Coarse-grained Monte-Carlo simulations of nanogel-polyelectrolyte complexes have been carried out. The results presented here capture two phenomena reported in experiments with real complexes: (i) the reduction in size after absorbing just a few chains and (ii) the charge inversion detected through electrophoretic mobility data. Our simulations reveal that charge inversion occurs if the polyelectrolyte charge is large enough. In addition, the distribution of chains inside the nanogel strongly depends on whether charge inversion takes place. It should also be stressed that the chain topology has little influence on most of the properties studied here.

Maximizing the absorption of small cosolutes inside neutral hydrogels: steric exclusion versus hydrophobic adhesion.

In this work the equilibrium absorption of nanometric cosolutes (which could represent drugs, reactants, small globular proteins and other kind of biomacromolecules) inside neutral hydrogels is studied. We specially focus on exploring, for different swelling states, the competition between the steric exclusion induced by the cross-linked polymer network constituting the hydrogel, and the solvent-induced short-range hydrophobic attraction between the polymer chains and the cosolute particle. For this purpose, the cosolute partition coefficient is calculated by means of coarse-grained grand canonical Monte Carlo simulations, and the results are compared to theoretical predictions based on the calculation of the excluded and binding volume around the polymer chains. For small hydrophobic attractions or large cosolute sizes, the steric repulsion dominates, and the partition coefficient decreases monotonically with the polymer volume fraction, ϕm. However, for large enough hydrophobic attraction strength, the interplay between hydrophobic adhesion and the steric exclusion leads to a maximum in the partition coefficient at certain intermediate polymer density. Good qualitative and quantitative agreement is achieved between simulation results and theoretical predictions in the limit of small ϕm, pointing out the importance of geometrical aspects of the cross-linked polymer network, even for hydrogels in the swollen state. In addition, the theory is able to predict analytically the onset of the maximum formation in terms of the details of the cosolute-monomer pair interaction, in good agreement with simulations too. Finally, the effect of the many-body attractions between the cosolute and multiple polymer chains is quantified. The results clearly show that these many-body attractions play a very relevant role determining the cosolute binding, enhancing its absorption in more than one order of magnitude.