Molecular insights into inclusion complex formation between β- and γ-cyclodextrins and rosmarinic acid

Abstract

In this study, we have investigated the stable inclusion complexes (IC) formation between β- and γ-cyclodextrin (γ-CyD) with rosmarinic acid (RA), a substance known to have antioxidant and anti-inflammatory effects. The β- and γ-CyD: RA ICs were prepared and characterized using experimental (1H NMR, FTIR, ICD and XRD, SEM) and computational techniques, such as molecular dynamics simulations and molecular docking. The thermodynamic parameter analysis showed that the formation of these ICs with the 1:1 molar ratio (AL type) and also, the apparent stability constant (KC) for β- and γ-CyD: RA ICs at 25 °C, were 79.07 ± 13.84 and 63.62 ± 9.31 L mol−1 respectively. Moreover, these results indicated that the encapsulation RA into the cavity of β- and γ-CyD: RA are exothermic (ΔH0 < 0) driven by the hydrophobic force and H-bond formations. Additionally, the experimental and theoretical methods confirmed that the β-CyD: RA IC is more stable than γ-CyD: RA IC. The computational results also confirm the formation of two stable IC. These results indicated that β- and γ-CyDs are promising excipients to formulate different substances, including RA to potentiate its antioxidant and anti-inflammatory activity bioavailability, solubility, and stability.