Molecular Modeling of Isoniazid Encapsulation by β-Cyclodextrin for Drug Delivery: Molecular Dynamics, Interaction Energies, and DFT Insights
7 affiliations
- 1Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, Egypt
- 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt
- 3Department of Supportive Requirements, University of Technology and Applied Sciences, Nizwa 611, Oman
- 4Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
- 5Central Laboratory, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
- 6Department of Biological, Chemical and Global Health Sciences, School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt
- 7School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa
Abstract
β-cyclodextrin (β-CD) plays a crucial role in advanced drug delivery processes, with potential applications in drug protection and release modulation. Therefore, the encapsulation potential of β-CD towards isoniazid (ISO) was herein comprehensively examined by performing molecular dynamics (MD) simulation with density functional theory (DFT) calculations. From an energetic perspective, the encapsulation process within the ISO⋯β-CD complex was energetically preferable, as evidenced by the negative interaction energy (Eint) values of configurations A–E. Compared to the other configurations, configuration A exhibited the most favorable Eint, reaching −41.66 kcal/mol. From FMO and TDOS analyses, a reduction in energy gap values was observed following the encapsulation process, indicating a change in the electronic structure of the ISO⋯β-CD complex. The effect of water on the encapsulation process within the ISO⋯β-CD complex was investigated. Furthermore, the potential release of ISO from β-CD was qualitatively assessed using simplified recovery-time estimates. Moreover, ISO adsorption over the β-CD surface was examined using the same approaches as the encapsulation model; however, it was energetically less favorable, with Eint values reaching only −18.42 kcal/mol. Overall, the MD-enhanced DFT results underscored the potential of β-CD as a candidate platform for ISO drug encapsulation; however, experimental validation is required to establish loading efficiency, release behavior, bioavailability, and toxicity.
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BibTeX
@article{rady2026molecular,
title = {{Molecular Modeling of Isoniazid Encapsulation by β-Cyclodextrin for Drug Delivery: Molecular Dynamics, Interaction Energies, and DFT Insights}},
author = {Al-shimaa S. M. Rady and Peter A. Sidhom and Shaista Zarrin Khanam and Mohamed K. Abd El-Rahman and Lamiaa A. Mohamed and Shaban R. M. Sayed and Tamer Shoeib and Mahmoud A. A. Ibrahim},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219838},
url = {https://www.mdpi.com/1422-0067/27/21/9838},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular Modeling of Isoniazid Encapsulation by β-Cyclodextrin for Drug Delivery: Molecular Dynamics, Interaction Energies, and DFT Insights
AU - Al-shimaa S. M. Rady
AU - Peter A. Sidhom
AU - Shaista Zarrin Khanam
AU - Mohamed K. Abd El-Rahman
AU - Lamiaa A. Mohamed
AU - Shaban R. M. Sayed
AU - Tamer Shoeib
AU - Mahmoud A. A. Ibrahim
PY - 2026
DA - 2026/11/03
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219838
UR - https://www.mdpi.com/1422-0067/27/21/9838
AB - β-cyclodextrin (β-CD) plays a crucial role in advanced drug delivery processes, with potential applications in drug protection and release modulation. Therefore, the encapsulation potential of β-CD towards isoniazid (ISO) was herein comprehensively examined by performing molecular dynamics (MD) simulation with density functional theory (DFT) calculations. From an energetic perspective, the encapsulation process within the ISO⋯β-CD complex was energetically preferable, as evidenced by the negative interaction energy (Eint) values of configurations A–E. Compared to the other configurations, configuration A exhibited the most favorable Eint, reaching −41.66 kcal/mol. From FMO and TDOS analyses, a reduction in energy gap values was observed following the encapsulation process, indicating a change in the electronic structure of the ISO⋯β-CD complex. The effect of water on the encapsulation process within the ISO⋯β-CD complex was investigated. Furthermore, the potential release of ISO from β-CD was qualitatively assessed using simplified recovery-time estimates. Moreover, ISO adsorption over the β-CD surface was examined using the same approaches as the encapsulation model; however, it was energetically less favorable, with Eint values reaching only −18.42 kcal/mol. Overall, the MD-enhanced DFT results underscored the potential of β-CD as a candidate platform for ISO drug encapsulation; however, experimental validation is required to establish loading efficiency, release behavior, bioavailability, and toxicity.
SN - 1422-0067
ER -