Enhancing Allicin bioavailability by way of cyclodextrin encapsulation: simulation and experiments

This study investigates the compatibility, inclusion stability, and solubility of Allicin with three types of cyclodextrins (β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), and 2,6-dimethyl-β-cyclodextrin (DM-β-CD)), using molecular simulation and experimental methods. Molecular dynamics simulations were employed to calculate solubility parameters, binding energy, mean square displacement, and hydrogen bonding of the three inclusion complexes (ICs). The mixing energy was calculated using Monte Carlo simulations. The smallest difference in solubility parameters was observed between DM-β-CD and Allicin, indicating superior compatibility. DM-β-CD exhibited the highest binding energy and strongest interaction, signifying greater inclusion stability. Fourier transform infrared spectrometry, X-ray diffraction, and differential scanning calorimetry analyses confirmed the successful formation of the three ICs. Phase solubility tests revealed that all three cyclodextrins formed 1:1 IC with Allicin, consistent with the simulated IC model. DM-β-CD and Allicin demonstrated higher solubility, indicating the best compatibility. Compared with pure Allicin, the solubility of Allicin increased by 5.6 times, 17.59 times, and 12 times in the Allicin/β-CD IC, Allicin/DM-β-CD IC, and Allicin/HP-β-CD IC, respectively. Inclusion stability constant (K_s) value for Allicin/DM-β-CD IC was the highest at 1555.9 M⁻¹. These results indicate that the Allicin/DM-β-CD ICs exhibit the best stability, which is consistent with the simulation findings.