Multianalytical and Theoretical Tendency for the Clarification of the Binding of Lansoprazole and Albumin Protein

Understanding the interaction between pharmaceutical agents and serum albumin is critical for assessing drug bioavailability, distribution, and pharmacokinetics. In this study, the binding mechanism of lansoprazole (LAN) to bovine serum albumin (BSA) was systematically investigated using spectroscopic, electrochemical, and computational approaches. Fluorescence quenching experiments showed that the interaction follows a dynamic quenching mechanism and a moderate affinity, revealing a binding constant of 1.25, 2.76, and 5.24 × 10⁴ M^-1 for 287, 298, and 307 K, respectively. Thermodynamic analysis revealed that the binding process is predominantly driven by hydrophobic interactions, as supported by positive enthalpy (ΔH) and entropy (ΔS) values. UV-vis absorption spectroscopy confirmed structural changes in BSA upon LAN binding, while three-dimensional fluorescence spectroscopy showed changes in the microenvironment of tryptophan and tyrosine residues. Electrochemical studies also supported the formation of a stable, nonelectroactive LAN-BSA complex, leading to decreased peak currents. Molecular docking and molecular dynamics simulations provided atomic-level information, showing that LAN preferentially binds to the I site of BSA, stabilized by hydrogen bonding and hydrophobic interactions. Circular dichroism spectral results indicated a secondary structural change in HSA upon LAN binding. The findings of this study contribute to a better understanding of the pharmacokinetic behavior of LAN, providing valuable information about its therapeutic efficacy and potential drug-protein interactions.