Investigation of Cannabinoid Acid/Cyclodextrin Inclusion Complex for Improving Physicochemical and Biological Performance
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. HPLC Analysis of Cannabinoids
2.3. Phase Solubility Studies of Cannabinoids According to the Types of Cyclodextrin
2.4. Preparation of Cannabinoids/M-β-CD Inclusion Complex
2.5. Solid-State Characterization of Cannabinoids and Cyclodextrin Inclusion Complex
2.5.1. Determination of Cannabinoid Solubility
2.5.2. Field-Emission Scanning Electron Microscopy (FE-SEM)
2.5.3. Differential Scanning Calorimetry (DSC)
2.5.4. X-ray Diffraction (XRD)
2.6. Proton Nuclear Magnetic Resonance (1H NMR) Spectroscopy
2.7. Stability Studies of the Inclusion Complex in Simulated Physiological Conditions
2.8. In Vitro Permeation Studies
2.9. In Vitro Anti-Cancer Activity Assay Using Human Breast (MCF-7) Cancer Cell Lines
3. Results and Discussion
3.1. Phase Solubility Studies of Cannabinoids According to Types of Cyclodextrin
3.2. Solid-State Characterization of Cannabinoids and CD Inclusion Complex
3.2.1. Solubility Determination
3.2.2. FE-SEM Analysis
3.2.3. DSC Analysis
3.2.4. XRD Analysis
3.3. 1H NMR Studies of Cannabinoids/M-β-CD Inclusion Complex
3.4. In Vitro Permeation Profiles of Cannabinoids/M-β-CD Inclusion Complex
3.5. Stability Profiles of Cannabinoid Acids and CD Inclusion Complex in Simulated Physiological Condition
3.6. In Vitro Anti-Cancer Activities of Cannabinoids/M-β-CD Inclusion Complex
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CD | cyclodextrin |
α-CD | α-cyclodextrin |
β-CD | β-cyclodextrin |
γ-CD | γ-cyclodextrin |
HP-α-CD | hydroxypropyl-α-cyclodextrin |
M-β-CD | methylated-β-cyclodextrin; |
DSC | differential scanning calorimetry |
FE-SEM | field-emission scanning electron microscopy |
1H NMR | proton nuclear magnetic resonance spectroscopy |
THC | tetrahydrocannabinol |
CBD | cannabidiol |
THCA | Tetrahydro-cannabinolic acid |
CBDA | cannabidiolic acid |
COX | cyclooxygenase |
RP | reversed-phase |
HPLC | high-performance liquid chromatographic system |
PVDF | Polyvinylidene Fluoride |
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Types of Cannabinoid Acid | Types of Cyclodextrin | Slope | Y-Intercept (So, mM) | Stability Constant (KS, M−1) | Regression Coefficient (R2) | Complexation Efficiency (%) | Molar Ratio (Cannabinoids:CD) |
---|---|---|---|---|---|---|---|
THCA | α-CD | 0.086 | 0.052 | 642 | 0.998 | 9.43 | 1.00:11.39 |
β-CD | 0.262 | 0.359 | 2140 | 0.997 | 35.5 | 1.00:3.80 | |
γ-CD | 0.096 | 0.109 | 1280 | 0.998 | 10.6 | 1.00:10.38 | |
M-β-CD | 0.344 | 0.448 | 2360 | 0.999 | 52.5 | 1.00:2.88 | |
HP-β-CD | 0.227 | 0.241 | 1400 | 0.999 | 29.4 | 1.00:4.35 | |
CBDA | α-CD | 0.098 | 0.018 | 191 | 0.998 | 10.8 | 1.00:10.27 |
β-CD | 0.115 | 0.018 | 159 | 0.997 | 13.0 | 1.00:8.64 | |
γ-CD | 0.185 | 0.035 | 199 | 0.998 | 22.6 | 1.00:5.45 | |
M-β-CD | 0.390 | 0.141 | 420 | 0.999 | 63.9 | 1.00:2.55 | |
HP-β-CD | 0.138 | 0.023 | 172 | 1.000 | 15.9 | 1.00:7.25 |
Types of Cannabinoids | Ratio of EtOH/Water | Inclusion Complex | |
---|---|---|---|
Drug Loading Content (%) | Molar Ratio | ||
THCA | 20% EtOH (v/v) | 11.05 ± 0.02 | 1:1.93 |
15% EtOH (v/v) | 11.18 ± 0.03 | 1:1.91 | |
10% EtOH (v/v) | 8.37 ± 0.01 | 1:2.62 | |
5% EtOH (v/v) | 4.98 ± 0.02 | 1:4.58 | |
2.5% EtOH (v/v) | 2.38 ±0.04 | 1:9.82 | |
CBDA | 20% EtOH (v/v) | 10.51 ± 0.05 | 1:2.27 |
15% EtOH (v/v) | 12.25 ± 0.09 | 1:1.72 | |
10% EtOH (v/v) | 5.34 ± 0.01 | 1:4.26 | |
5% EtOH (v/v) | 2.83 ± 0.00 | 1:8.25 | |
2.5% EtOH (v/v) | 1.02 ± 0.01 | 1:23.28 |
Preparation Method | Types of Cannabinoids | Aqueous Solubility of Cannabinoid Acids (µg/mL) | ||
Molar Ratio (Cannabinoids: M-β-CD) | ||||
1:1 | 1:2 | 1:5 | ||
Spray-drying | THCA | 220 ± 9 | 480 ± 20 | 338 ± 3 |
CBDA | 300 ± 70 | 554 ± 4 | 440 ± 10 | |
Freeze-drying | THCA | 78 ± 5 | 190 ± 10 | 110 ± 30 |
CBDA | 93 ± 8 | 200 ± 20 | 90 ± 10 | |
Spray-freeze-drying | THCA | 310 ± 20 | 930 ± 20 | 470 ± 60 |
CBDA | 450 ± 40 | 1090 ± 40 | 540 ± 60 |
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Park, C.; Zuo, J.; Gil, M.-C.; Löbenberg, R.; Lee, B.-J. Investigation of Cannabinoid Acid/Cyclodextrin Inclusion Complex for Improving Physicochemical and Biological Performance. Pharmaceutics 2023, 15, 2533. https://doi.org/10.3390/pharmaceutics15112533
Park C, Zuo J, Gil M-C, Löbenberg R, Lee B-J. Investigation of Cannabinoid Acid/Cyclodextrin Inclusion Complex for Improving Physicochemical and Biological Performance. Pharmaceutics. 2023; 15(11):2533. https://doi.org/10.3390/pharmaceutics15112533
Chicago/Turabian StylePark, Chulhun, Jieyu Zuo, Myung-Chul Gil, Raimar Löbenberg, and Beom-Jin Lee. 2023. "Investigation of Cannabinoid Acid/Cyclodextrin Inclusion Complex for Improving Physicochemical and Biological Performance" Pharmaceutics 15, no. 11: 2533. https://doi.org/10.3390/pharmaceutics15112533
APA StylePark, C., Zuo, J., Gil, M.-C., Löbenberg, R., & Lee, B.-J. (2023). Investigation of Cannabinoid Acid/Cyclodextrin Inclusion Complex for Improving Physicochemical and Biological Performance. Pharmaceutics, 15(11), 2533. https://doi.org/10.3390/pharmaceutics15112533