Molecular dynamics, quantum mechanical and semi-empirical investigations of paclitaxel-containing oil-in-water pluronic F127 and lignin microemulsions

• Paclitaxel (PTX)-loaded Pluronic F127 and lignin microemulsions were studied by DFT. • Alteration of atomic charges due to hydrogen bonding and charge transfer influence the stability of PTX-loaded microemulsions. • Electron charge transfer between molecular orbitals of the surfactants and PTX was analysed. • Binding energies of the F127-PTX complexes were larger than those of lignin-PTX ones. Oil-in-water microemulsions based on surfactants F127 and lignin may enhance the availability of Paclitaxel (PTX) in bio-systems that lead to improved drug delivery. Therefore, PTX-loaded microemulsions were designed by means of molecular dynamics (MD) simulations, density functional theory (DFT), and semi-empirical methods. The MD simulations revealed a more stable release of PTX in microemulsion form compared to the bulk one (free drug). Quantum mechanics calculations pointed out that stability of the PTX-F127 microemulsions are higher compared to PTX-Lignin ones. Furthermore, hydrogen bond (HB) forces help to ensure the stability of the PTX-surfactants in microemulsions. Alteration of atomic charges due to hydrogen bond forces and charge transport (CT) influence the stability of the PTX-loaded microemulsions. HB interactions appeared to play an important role on the improved action of PTX in microemulsion systems compared to free drug. The delivery of PTX in microemulsion systems is attributable to the exchange interactions between surfactants and PTX. The semi-empirical calculations showed that the heat of formation values (ΔH f ) of the PTX-F127 complexes are larger (more negative) than those for the PTX-Lignin ones.