Nghiên cứu mô phỏng DFT tính chất hấp phụ và giải hấp phụ trong dung môi nước của Luteolin và Ambroxol trên Cyclodextrin

Cyclodextrins, particularly β-cyclodextrin (β-CD), are widely recognized as versatile pharmaceutical excipients, playing a crucial role in enhancing drug solubility, stability, and bioavailability through the formation of inclusion complexes. Understanding the intricate molecular interactions governing drug loading and release from these carriers is paramount for optimizing drug delivery systems. This study leverages Density Functional Theory (DFT) simulations, a powerful computational tool, to comprehensively investigate the adsorption and desorption behaviors of two key active compounds, luteolin and ambroxol, with β-CD in an aqueous environment. The research specifically aims to elucidate the fundamental mechanisms that dictate the encapsulation and subsequent release of these drugs, offering critical insights into the design of more effective drug delivery vehicles.

Researchers in computational chemistry, pharmaceutical science, drug design and delivery, and materials science interested in host-guest interactions and cyclodextrin applications.

This research comprehensively explores the adsorption and desorption properties of luteolin (a polyphenol) and ambroxol (an amine-type drug) within β-cyclodextrin (β-CD) in aqueous solution using Density Functional Theory (DFT). Employing the M06-2X functional with the 6-311G(d) basis set and empirical dispersion (GD3) in Gaussian 16 software, the study meticulously characterized the interaction structures and calculated the thermodynamic parameters. The computational results unequivocally demonstrate that the adsorption of both luteolin and ambroxol onto β-CD is a highly favorable, spontaneous, and exothermic process, evidenced by significant negative Gibbs free energy (∆G°) and enthalpy (∆H°) values. Specifically, the most stable configurations for luteolin exhibited ∆G°/∆H° values of -22.7/-40.5 kcal/mol, while ambroxol showed values of -16.3/-32.1 kcal/mol. Hydrogen bonding was identified as the primary stabilizing force within these inclusion complexes. A critical aspect of this study involved investigating the potential for desorption at target proteins, specifically angiotensin I and II, by comparing interaction energies with amino acid residues like Asparagine (Asp) and Tyrosine (Tyr). Findings indicate that β-CD is unable to desorb luteolin at the investigated specific amino acid sites. However, ambroxol can be successfully desorbed from β-CD at the Tyr site, suggesting a differential release mechanism based on the drug's nature. These insights are invaluable for predicting and optimizing β-CD’s utility as a targeted drug carrier, particularly in developing controlled drug release formulations where specific interaction with biological targets is desired.