Molecular analysis of interactions between a PAMAM dendrimer-paclitaxel conjugate and a biomembrane

Understanding the underlying mechanism of nanomedicine-biomembrane interactions is important for the design and optimization of payload delivery systems. This study investigates the interactions between polyamidoamine (PAMAM) dendrimer-paclitaxel conjugates and biomembranes using coarse-grained molecular dynamics simulations. We found that acidic conditions (e.g., pH ∼ 5) and membrane asymmetry can improve the conjugate penetration. Paclitaxel (PTX) distributions on a G4 PAMAM dendrimer can affect interactions via the penetration mechanism, although they have no significant effect on interactions via the adsorption mechanism. The random distribution of PTX can enhance the ability of PTX molecules to pass through asymmetric membranes. Furthermore, the penetration process becomes more difficult with increasing paclitaxel loading ratios. These results provide molecular insights into the precise translocation mechanism of dendrimer-drug conjugates and thus provide suggestions for drug design and delivery.