A molecular dynamics insight into the encapsulation behavior of carmustine and fluorouracil drugs on MgO nanotubes as a novel and efficient nanocarrier

• Studies examining the bulk characteristics of Magnesium oxide (MgO) nanotubes via molecular dynamics simulation have only recently attracted interest. • Magnesium oxide (MgO) nanotubes, with their biocompatibility, large surface area, and high surface reactivity, can act as antibacterial agents in cancer treatment and have a synergistic effect with Carmustine and Fluorouracil in cancer treatment. • Competition between two anticancer drugs, Carmustine and Fluorouracil, in terms of encapsulation rate and binding energy. • New aspects of structural parameters in the interaction between drug and MgO nanotube and its self-aggregation behavior. In this research, the computational method of molecular dynamics simulation was employed to investigate the adsorption of Carmostine and Fluorouracil, two drugs, onto the MgO nanotube as an efficient drug delivery system. It focuses on structural properties, drug loading capacity in the carrier, intermolecular interactions, and drug encapsulation behaviors. The molecular structure of drugs was obtained from the PubChem database. Primary structures in molecular dynamics using Gaussian09 software in an aqueous environment at DFT/B3LYP/6-31g(d) level of theory were optimized. The restrained electrostatic potential method was used to calculate partial charges. Basic parameters were built into the tleap code in the AmberTools package. The GROMACS 2024 software, a modified water model (SPC/E), and the Amber99SB force field were used in all-atom simulations. VMD and Chimera packages were used to view simulation photos. The root means square deviation values predict that fluorouracil has greater dynamic stability than carmustine. The results of the radial distribution function and density distribution of the drug molecule around the MgO nanocarrier predict well that the maximum distribution of the carmustine drug molecule is around the nanocarrier and in the case of fluorouracil, the maximum distribution is in the center of mass of the nanocarrier. These studies show that the fluorouracil drug molecule penetrates well into the nanocarrier and its main distribution is in the center of mass of the nanocarrier, and this can be used in slow-release or extended-release. The Gibbs free energy of binding of Carmostine and Fluorouracil on MgO nanotube carrier at 310 K and in the NPT ensemble according to the Poisson Boltzmann surface area method was obtained as -20.19±0.24 and -16.15±0.11 kcal/mol, respectively, and according to these values, it can be concluded that the process loading or encapsulation of Carmostine and Fluorouracil in the carrier are thermodynamically favorable.