Drug-Loading Capacity of PAMAM Dendrimers Encapsulating Quercetin Molecules: A Molecular Dynamics Study with the 2016H66 Force Field.

The complexation of quercetin molecules with poly(amidoamine) (PAMAM) dendrimers of generation 0-3 was studied by molecular dynamics simulations. Three main points were addressed: (i) the effect of starting from different initial structures; (ii) the performance of the 2016H66 force field (recently validated in the context of dendrimer simulations) in predicting the experimental drug(quercetin)-loading capacity of PAMAM dendrimers; and (iii) the stability of quercetin-PAMAM complexes and their interactions. Initial structures generated by different restraint protocols led to faster convergence compared to initial structures generated by randomly placing the drug molecules in the simulation box. The simulations yielded meta-stable complexes where the loading numbers have converged to average values and were compared to experimentally obtained values. Once the first meta-stable state was reached, the drug-dendrimer complexes did not deviate significantly throughout the simulation. They were characterized in terms of structural properties, such as the radius of gyration and radial distribution functions. The results suggest that quercetin molecules interact mostly with the internal dendrimer monomers rather than to their surface.