Amorphous Inclusion Complexes: Molecular Interactions of Hesperidin and Hesperetin with HP-Β-CD and Their Biological Effects
Abstract
:1. Introduction
2. Results
2.1. Preparation of Systems of Hesperidin and Hesperetin with HP-β-CD
2.2. Identification of Hesperidin and Hesperetin with HP-β-CD Systems
2.2.1. Fourier Transform Infrared Spectroscopy
2.2.2. X-ray Powder Diffraction
2.2.3. Differential Scanning Calorimetry
2.3. Physicochemical Properties
2.3.1. Solubility Studies
2.3.2. Dissolution Rate Studies
2.3.3. Permeability Studies
2.4. Biological Assays
2.4.1. Antioxidant Activity Assay
2.4.2. Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) Inhibition Assay
2.5. Docking
2.6. Molecular Dynamics
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Preparation of the Systems
4.3. Identification of Obtained Systems
4.3.1. Fourier Transform Infrared Spectroscopy and Density Functional Theory (DFT) Calculations
4.3.2. X-ray Powder Diffraction
4.3.3. Differential Scanning Calorimetry
4.4. Physicochemical Properties
4.4.1. Solubility Studies
Media for Solubility and Dissolution Rate Studies
Solubility Studies
4.4.2. Dissolution Studies
4.4.3. Permeability Studies
4.5. Biological Assays
4.5.1. Antioxidant Activity Assay
4.5.2. Determination of Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) Inhibition
4.6. Docking
4.7. Molecular Dynamics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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System | Concentration (mg·mL−1) (↑-Improvement of Solubility (Fold)) | ||
---|---|---|---|
Water | Phosphate Buffer pH 6.8 | HCl 0.1 N | |
Hed | 0.009 ± 0.001 | 0.009 ± 0.002 | 0.008 ± 0.003 |
Hed/HP-β-CD 1:1 | 1.709 ± 0.012 (↑190) | 1.861 ± 0.023 (↑207) | 1.663 ± 0.004 (↑208) |
Hed/HP-β-CD 1:2 | 9.280 ± 0.011 (↑1031) | 10.588 ± 0.073 (↑1176) | 9.000 ± 0.043 (↑1125) |
Hed/HP-β-CD 1:1 PM | 0.439 ± 0.003 (↑49) | 0.432 ± 0.001 (↑48) | 0.396 ± 0.0003 (↑50) |
Hed/HP-β-CD 1:2 PM | 0.679 ± 0.001 (↑75) | 0.692 ± 0.001 (↑77) | 0.605 ± 0.0005 (↑76) |
Het | 0.008 ± 0.0001 | 0.015 ± 0.0002 | 0.006 ± 0.0001 |
Het/HP-β-CD 1:1 | 6.965 ± 0.021 (↑871) | 7.018 ± 0.042 (↑468) | 6.238 ± 0.015 (↑1040) |
Het/HP-β-CD 1:2 | 12.546 ± 0.091 (↑1568) | 12.756 ± 0.097 (↑850) | 12.933 ± 0.028 (↑2156) |
Het/HP-β-CD 1:1 PM | 1.401 ± 0.002 (↑175) | 2.401 ± 0.003 (↑160) | 1.642 ± 0.001 (↑274) |
Het/HP-β-CD 1:2 PM | 2.826 ± 0.001 (↑353) | 4.969 ± 0.002 (↑331) | 3.750 ± 0.004 (↑625) |
Guest–Host Interactions | Hesperidin + β-CD | Hesperidin + 2HP-β-CD* | Hesperidin + 2HP-β-CD# | Hesperetin + β-CD | Hesperetin + 2HP-β-CD* | Hesperetin + 2HP-β-CD# |
---|---|---|---|---|---|---|
Lennard–Jones (kJ/mol) | −100.2 | −117.6 | −129.6 | −92.7 | −102.4 | −106.3 |
Coulombic (kJ/mol) | −25.8 | −40.2 | −54.3 | −14.1 | −24.6 | −15.1 |
Hydrogen bonding (occurrence/timeframe) | 0.653 | 1.366 | 2.079 | 0.194 | 1.024 | 0.592 |
SASA (nm2) | −4.18 | −6.04 | −6.52 | −4.13 | −5.17 | −4.47 |
Binding energy (kJ/mol) | −23.4–−20.5 | −24.7–−20.5 | −28.5–−25.5 | −26.4–−24.3 | −28.0–−26.4 | −30.5–−29.3 |
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Wdowiak, K.; Rosiak, N.; Tykarska, E.; Żarowski, M.; Płazińska, A.; Płaziński, W.; Cielecka-Piontek, J. Amorphous Inclusion Complexes: Molecular Interactions of Hesperidin and Hesperetin with HP-Β-CD and Their Biological Effects. Int. J. Mol. Sci. 2022, 23, 4000. https://doi.org/10.3390/ijms23074000
Wdowiak K, Rosiak N, Tykarska E, Żarowski M, Płazińska A, Płaziński W, Cielecka-Piontek J. Amorphous Inclusion Complexes: Molecular Interactions of Hesperidin and Hesperetin with HP-Β-CD and Their Biological Effects. International Journal of Molecular Sciences. 2022; 23(7):4000. https://doi.org/10.3390/ijms23074000
Chicago/Turabian StyleWdowiak, Kamil, Natalia Rosiak, Ewa Tykarska, Marcin Żarowski, Anita Płazińska, Wojciech Płaziński, and Judyta Cielecka-Piontek. 2022. "Amorphous Inclusion Complexes: Molecular Interactions of Hesperidin and Hesperetin with HP-Β-CD and Their Biological Effects" International Journal of Molecular Sciences 23, no. 7: 4000. https://doi.org/10.3390/ijms23074000