The drug loading behavior of PAMAM dendrimer: Insights from experimental and simulation study

Poly(amidoamine) (PAMAM) dendrimers are widely studied as drug vectors due to their particular structure and excellent properties. Drug molecules can be loaded in the internal cavity of dendrimers or adsorbed on the surface. In this paper, the interaction force and spatial configuration between PAMAM and several typical chemotherapy drugs (doxorubicin (DOX), paclitaxel (TAX), hydroxycamptothecin (HCPT)) is studied by molecular dynamics (MD) simulations. Several essential parameters of dendrimers as drug carriers are analyzed by combining experiments and MD simulations, including particle size, drug loading, drug release, and biocompatibility. The simulation of dendrimer@drug complexes demonstrates that many cavities are semi-open, and most drug molecules are not completely wrapped. The internal structure of PAMAM dendrimers became looser with more extended nuclei, which increased the non-covalent interactions between PAMAM dendrimers and drug molecules. The umbrella sampling simulations reveal that the change of binding energies between dendrimers and drug molecules is responsible for the variation in drug release rate. This study provides valuable enlightenment information for the drug loading/release of PAMAM dendrimers.