|
Computational Evaluation of Cyclodextrin–Amiodarone Inclusion Complexes: Implications for Solubility and off-Target Toxicity
|
F Fateminasab    , M Farahani , E Kianpour |
| Department of Physical Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran, , ftmfatemi61@gmail.com |
|
|
Abstract: (14 Views) |
Introduction: Amiodarone (AMD) is recognized as a potent antiarrhythmic drug that can exert toxic effects on thyroid cells and lead to thyroid dysfunction. This study investigates the protein target mechanisms associated with AMD-induced thyroid toxicity in the thyroid, as well as the application of cyclodextrins (CDs) to mitigate off-target adverse effects and drug toxicity in non-target tissues. Materials and Methods: To identify protein targets associated with AMD-related thyroid toxicity, the DGIdb and STITCH databases were employed, and targets overlapping with genes linked to “thyroid dysfunction” in the GeneCards database were extracted and their functions examined. To improve drug solubility, molecular interactions between modified cyclodextrins (hydroxypropyl-β-cyclodextrin (HP-βCD) and dimethyl-β-cyclodextrin (DM-βCD)) and AMD were evaluated using two approaches: molecular docking and molecular dynamics (MD) simulations. Results: Potential targets involved in the drug’s toxic effects and the induction of thyroid dysfunction were identified. Molecular docking results showed that the binding energies for the HP-βCD: AMD and DM-βCD: AMD inclusion complexes were −35.52 and −29.04 kJ·mol⁻¹, respectively, indicating a stronger interaction of HP-βCD with the drug. The total interaction energy analysis (sum of van der Waals and Coulombic terms) from MD simulations demonstrated that the HP-βCD complex exhibited higher stability with an energy of −157.97±17.32 kJ·mol⁻¹ compared to the DM-βCD: AMD complex at −149.40±12.98 kJ·mol⁻¹. Conclusion: HP-βCD appears to be a better nanocarrier for AMD encapsulation and targeted release due to its stronger interaction and higher stability, and may have significant potential to improve the pharmacokinetic properties and reduce side effects of this drug. These results are computational and require experimental confirmation. |
|
| Keywords: Amiodarone, Thyroid disorders/Dysfunction, Drug delivery, Modified Cyclodextrin, Molecular docking, Molecular dynamics simulation |
|
|
Full-Text [PDF 1531 kb]
(5 Downloads)
|
Type of Study: Original |
Subject:
Endocrinology
Received: 2025/08/15 | Accepted: 2025/11/23 | Published: 2025/03/30
|
|
|
|
|
|
|
| Add your comments about this article |
|
|
|
