Molecular dynamics insight into drug-loading capacity of dodecylphosphocholine aggregate for doxorubicin

Abstract

The therapeutic effect of doxorubicin (DOX) on various cancers is enticing, but its huge toxic side effects are equally obvious. Loading it into nanocarriers and then delivering the drug is currently the most promising solution. In this work, we investigate the assembly mechanism of dodecylphosphorylcholine (DPC) aggregates for encapsulating DOXs using molecular dynamics simulation with an all-atomic force field. The principal propellants of the drug encapsulation procedure encompass hydrophobic and van der Waals interactions. Additionally, hydrogen bonding and electrostatic interactions wield significant influence in the aggregation dynamics of DPCs. The radial distribution function indicates that when DPC aggregates act as stable carriers exerting strong adhesion to the drugs, intermolecular interactions predominantly manifest within the spatial interval ranging from 0.5 nm to 1.0 nm. All calculated data and visualized images of the system configuration changing with simulation time reveal that after about 30 ns, the changes in DPC aggregation sites tend to ultimately form multiple aggregates and exhibit a good morphology loaded with DOXs. Our study explored the drug-carrying potential of DPC, which provides an important theoretical basis and effective guidance for researchers to design a more suitable DDS for DOX and then break through the bottleneck of the clinical application of DOX.