Molecular dynamics, density functional theory and semi-empirical investigations about interactions of dobutamine and F127/lignin microemulsions

Dobutamine (Dobu) is a helpful inotropic agent for the short-term control of heart failure. F127 is a useful copolymer (PEO(100)–PPO(65)–PEO(100)) with low toxicity that is used for encapsulation of drugs. Also, Lignin is a class of complex organic polymers that form fundamental structural materials in the support tissues of most plants. F127-based and Lignin-based oil-in-water microemulsions appear to increase the bioavailability of Dobu and cause better release of this curative drug. Accordingly, Dobu-loaded microemulsions were investigated using molecular dynamics (MD) simulations, density functional theory (DFT), and semi-empirical methods. Atoms in molecules (AIM), localized molecular orbital energy decomposition analysis (LMO-EDA), and aromaticity benchmark were used to investigate the nature of interactions between surfactants and Dobu. Results suggest that the F127/Dobu complexes are more stable than the Lignin/Dobu ones. The MD simulations reveal the existence of more hydrogen bond (HB) interactions in the F127/Dobu complexes compared to the Lignin/Dobu ones. Moreover, the stable delivery of Dobu from microemulsions can be related to the exchange interactions between the surfactants and this Drug. Results also reveal that there are HB interactions between the surfactants and Dobu, which stabilize the microemulsion system and yield the better performance of Dobu in microemulsions compared to free drug. The semi-empirical study discloses that the sum of intermolecular HB distance (d HB ) values in the F127/Dobu complexes is shorter compared to the Lignin/Dobu ones. • Dobutamine-loaded Pluronic F127 and lignin microemulsions were studied by MD, DFT and semi-empirical methods. • More hydrogen bonds were formed during the simulation for F127/Dobutamine complexes compared to the Lignin/Dobutamine ones. • Binding energies of the F127-Dobutamine complexes were larger than those of lignin-Dobutamine ones. • Strong interaction of Dobu and F127 was observed, which is expected to cause a great drug loading in the microemulsion.