Exploring the mechanisms of drug-delivery by decorated ZnO nanoparticles through predictive ReaxFF molecular dynamics simulations.

Herein, we study the assembling of a drug delivery nanocarrier through reactive molecular dynamics simulations based on an appropriately tuned force field. First, we focus on the combination of the various components (all selected in agreement with experiments), namely nanoparticle (ZnO), functional chains (oleic acid), drug (carfilzomib), and solvent molecules (ethanol), and then on the ability of the assembled nanotool to release its cargo in a physiological environment (water). The simulation results reveal that reactivity is crucial for characterizing the stability of the functionalized ZnONP, its dynamics, and its interactions with lipid chains and drug molecules. The chains are stably chemisorbed on the ZnONP through monodentate or bidentate binding of the carboxyls to the Zn atoms (the hydrogens are released to the surface oxygens). Chains' self-interactions reinforce the lipid cover's stability and distribution on the ZnONP interface. The added drug migrates from the solution to the nano assembly and is captured by the lipids. The molecules are entrapped among the oleic acid chains and adsorbed on the uncoated regions of the nanoparticle surface, partially physisorbed or chemisorbed. The analysis of the simulations confirms that the supramolecular assembly is compact and stable in ethanol. However, upon injection into the water, the size of the aggregate gradually increases, and the lipids start to swell with the aqueous medium. The system evolves towards an unpacked structure where the chains are elongated, separated, and prone to release the cargo depending on local water activity and depth of cargo insertion. All the results agree with the literature confirming the reliability of our predictive computational procedure for disclosing the structure and dynamics of complex materials relevant to the medicinal chemistry field.