Molecular Dynamics Simulation of PAMAM Dendrimer-Drug Delivery Systems

Dendrimers are viewed as hyperbranched, three-dimensional, monodisperse globular macromolecules with branches emanating from each monomeric unit. For improving the solvability of hydrophobic drugs and raising their bioactivity accompanied by a persistent release action, dendrimeric nanoparticles are customarily employed as latent drug delivery devices. PAMAM dendrimers have been broadly investigated as new approaches for restrained drug delivery; nevertheless, the computational analysis of the dendrimer-drug complex is an intricate phenomenon ascribable to the conformational flexibility of dendrimers and the distinct characteristics of the interactions existing within the dendrimer-drug system. Traditional procedures for analyzing drug interaction have been intended mainly for protein-derived substrates and, thus, there is a necessity to create novel conventions to handle special views of dendrimers. In the present research investigation, cavities in generation-2 and generation-3 Polyamidoamine (PAMAM) dendrimers have been developed, followed by the employment of fully atomistic molecular dynamics (MD) simulations to analyze the interactions of dendrimer with multitudinous model drugs, encompassing Tricaprin, Cinnamide, and Chloramphenicol palmitate (CAP-P). The binding energies, along with the energies associated with highest occupied molecular orbital, lowest unoccupied molecular orbital, and energy gap values have been assessed for various dendrimeric (PAMAM)-drug complexes and it was ascertained that it was energetically feasible for the drug moieties to bind with the dendrimeric system. Among the multitudinal model drugs examined, it was found that CAP-P exhibited the greatest binding energy (− 13.09 kcal/mol), and lowest energy gap values of 6.32 eV toward G2 dendrimer, thereby signifying that PAMAM G2 was a suitable vehicle to carry CAP-P drug possessing greater reactivity, with reduced system stability.