Oil-in-water nanoemulsions comprising Berberine in olive oil: biological activities, binding mechanisms to human serum albumin or holo-transferrin and QMMD simulations

Berberine is widely used in traditional Iranian medicine to treat diabetes and inflammatory conditions. This study was aimed at developing a method for the preparation of Berberine nanoparticles (Nano-Ber) in order to improve its aqueous-phase solubility and its complex formation with human serum albumin (HSA) and holo-transferrin (HTF) from the viewpoint of interaction behavior. Nano-Ber was prepared with olive oil as the oil phase, Tween 80 as the surfactant and Span 60 as the co-surfactant. Nano-Ber was obtained with a spherical shape and a mean particle size of 43.7 +/- 3.6 nm, with an optimal oil:surfactant:co-surfactant ratio of 1:2:2, w/w/w. The antioxidant activity of Nano-Ber in comparison with Berberine was tested using DPPH and it was found that Nano-Ber had a large antioxidant activity. The cytotoxicity effects of Nano-Ber and Berberine on HepG2 were compared by MTT assay and detected in the treated HepG2 cells at concentrations up to 0.1 mM. The binding constants of HSA-Nano-Ber and HTF-Nano-Ber complexes formation were (2.93 +/- 0.02) x 10(4) and (9.62 +/- 0.03) x 10(3) M-1, respectively. Hydrogen bonds and van der Waals interactions were the predominant forces in the HSA-Nano-Ber and HTF-Nano-Ber complexes, and the process of Nano-Ber binding HSA and HTF was driven by Delta H-0 = -122.76 kJ mol(-1), Delta S-0 = -325.49 J mol(-1)K(-1) for HSA and Delta H-0 = -125.09 kJ mol(-1), Delta S-0 = -43.37 J mol(-1)K(-1) for HTF. The results of the simulation demonstrated that the Nano-Ber molecules were stabilized on the surface of final aggregates through both hydrophilic and hydrophobic interactions. Communicated by Ramaswamy Sarma