Development, physicochemical characterization and antibacterial evaluation of the baicalin/sulfobutylether-β-cyclodextrin inclusion complex.

The growing spread of antibiotic resistance represents a significant challenge in the medical field, making the treatment of bacterial infections increasingly difficult. Therefore, current research is focused on studying new formulations containing natural antibacterial/antibiofilm agents that can act on both planktonic and sessile bacteria. In this study we developed a soluble formulation of the flavonoid baicalin (BA) by complexation with sulfobutylether-β-cyclodextrin (SBE-β-CD), designed for the treatment of ocular infections. The inclusion complex, prepared by lyophilization, showed a significant increase in BA solubility (110-times higher than free BA) and fast dissolution. In solution studies and the deeper physical-chemical characterization performed at solid state evidenced the formation of a 1:1 inclusion complex with high association constant (about 6000 M-1). Moreover, NMR spectroscopy and molecular docking simulations evidenced the deeper penetration of benzoyl and cinnamoyl moieties of BA within the macrocycle cavity, whilst the glucuronic residue remained out of the cavity but probably interacting with sulfobutyl groups of the CD. Biological in vitro studies were carried out to verify the activity of the free and complexed BA against Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae and Escherichia coli. High improvement of antibacterial and antibiofilm activity was observed for the inclusion complex respect to the free drug against both Gram + and Gram- bacteria strains assayed.