Molecular dynamics of paclitaxel interaction with cyclodextrin-modified core-shell micelles

Advances in nanotechnology in recent decades have spread to medicine and led to the emergence of nanotherapeutics that significantly increase the efficiency and reduce the side effects of drugs. One of the challenges in this field is increasing the solubility and targeted delivery of hydrophobic drugs. One approach to design nanoparticles for hydrophobic drugs loading is the use of cyclodextrins, which are capable of binding hydrophobic regions of small molecules via host-guest interactions. However, rational design of drug carriers requires studying the interactions between nanoparticles and drugs and assessing the effect of the bound drug on the surface properties of nanoparticles at the molecular level. In this work, we applied molecular dynamics simulations to study the interaction of core–shell micelles functionalized with alpha and beta CDs and a common drug, paclitaxel. Nanoparticle surfaces before and after interaction were analyzed using topographic mapping. It was found, that although paclitaxel molecules are able to partially penetrate into the cavities of both alpha and beta CD and form inclusion complexes, the fraction of molecules bound in this way is small, the majority of drug molecules ends up in cavities and grooves on the surface of the nanoparticles, the walls of which are lined with hydrophobic fragments of the spacer. In addition, paclitaxel molecules often cluster and adsorb on the surface of the hydrophobic core, but do not penetrate into it. The results obtained may be useful for the structure optimization and rational design of drug delivery systems.