Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Synthesis of the Star-like 4-Armed Copolymer
2.2.2. Size Exclusion Chromatography (SEC)
2.2.3. Proton Nuclear Magnetic Resonance (1H-NMR)
2.2.4. Preparation of Cannabidiol-Loaded Conventional and Sterically Stabilized Niosomes
2.2.5. Entrapment Efficiency
2.2.6. Size, Size Distribution, and Zeta Potential Evaluation
2.2.7. Cryogenic Transmission Electron Microscopy (cryo-TEM)
2.2.8. Carboxyfluorescein (CF) Release Studies
2.2.9. In Vitro Cannabidiol Release from Niosomes
2.2.10. Physical Stability Studies
2.2.11. Evaluation of Cytotoxicity of Cannabidiol and CBD-Loaded Conventional and Copolymer-Modified Niosomes
Cell Lines and Culture Conditions
MTT Colorimetric Assay
2.2.12. Proteome Profiler Analysis of Apoptosis and Inflammation Related Signal Transduction Key Proteins
3. Results and Discussion
3.1. Synthesis of Copolymers
3.2. Characterization of Conventional and Copolymer-Modified Niosomes
3.3. Carboxyfluorescein Release from Conventional and Copolymer-Modified Niosomes
3.4. In Vitro Release of Cannabidiol from Optimal Plain and Copolymer-Modified Niosomes
3.5. Physical Stability Evaluation
3.6. Cytotoxicity Studies
3.6.1. MTT—Assay
3.6.2. Proteome Profiler Analysis after Treatment with Free or Niosomal CBD
4. 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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Copolymer | Mn a (g/mol) | Mw b (g/mol) | Mw/Mn b | ||
---|---|---|---|---|---|
Topology | Composition c,d,e | Abbreviation | |||
Linear | R[(CL)9(PO)7(EEGE)23]2 | 9600 | 13,200 | 1.20 | |
Linear | R[(CL)9(PO)7(G)23]2 | 2F-3K | 5900 | - | - |
Star-like, 3-armed | R[(CL)6(PO)7(EEGE)23]3 | 13,400 | 17,700 | 1.22 | |
Star-like, 3-armed | R[(CL)6(PO)7(G)23]3 | 3F-3K | 8300 | - | - |
Star-like, 4-armed | R[(CL)5(PO)7(EEGE)23]4 | 17,200 | 14,100 | 1.17 | |
Star-like, 4-armed | R[(CL)5(PO)7(G)23]4 | 4F-3K | 10,400 | - | - |
Sample | SF:Chol (mol:mol) | Copolymer (mol %) | Dh (nm) ± SD | PDI ± SD | ζ-Potential (mV) ± SD | EE (%) CBD |
---|---|---|---|---|---|---|
Conventional niosomes | ||||||
S1 | Sp20:Chol (6:4) | - | 230 ± 4.2 | 0.26 ± 0.05 | −13.3 ± 1.9 | 65.8 ± 1.7 |
S2 | Sp80:Chol (6:4) | - | 180 ± 3.2 | 0.22 ± 0.05 | −26.6 ± 2.2 | 64.7 ± 1.6 |
S3 | Sp60:Chol (6:4) | - | 186 ± 2.8 | 0.4 ± 0.02 | −12.9 ± 1.7 | 80.3 ± 0.7 |
S4 | Tw60:Sp60:Chol (3:3:4) | - | 177 ±2.3 | 0.39 ± 0.03 | −11.9 ± 0.5 | 85.2 ± 2.3 |
S5 | Tw60:Sp60:Chol (3.5:3.5:3) | - | 150 ± 1.1 | 0.35 ± 0.07 | −10.3 ± 1.6 | 93.2 ± 2.1 |
S6 | Tw60:Sp60:Chol (3.5:3.5:3) (blank) | - | 133 ± 1.7 | 0.31 ± 0.09 | −11.2 ± 1.5 | - |
S7 | Tw60:Sp60:Chol3.5:3.5:3(unsonicated) | - | 387 ± 5.3 | 0.32 ± 0.02 | −11.9 ± 2.1 | 93.5 ± 1.8 |
S8 | Tw60:Sp60:Chol 3.5:3.5:3 (blank) (unsonicated) | - | 489 ± 3.8 | 0.34 ± 0.06 | −12.3 ± 2.3 | - |
Niosomes modified with 2F-3K | ||||||
S9 | Tw60:Sp60:Chol 3.5:3.5:3 | 0.5 | 224 ± 4.5 | 0.19 ± 0.02 | −12.2 ± 1.8 | - |
S10 | Tw60:Sp60:Chol 3.5:3.5:3 | 1 | 237 ± 6.9 | 0.26 ± 0.06 | −11.7 ± 0.6 | - |
S11 | Tw60:Sp60:Chol 3.5:3.5:3 | 2.5 | 250 ± 5.3 | 0.31 ± 0.05 | −10.1 ± 1.4 | - |
S12 | Tw60:Sp60:Chol 3.5:3.5:3 | 2.5 | 240 ± 3.3 | 0.38 ±0.03 | −11.3 ± 2.1 | 89.3 ± 2.1 |
Niosomes modified with 3F-3K | ||||||
S13 | Tw60:Sp60:Chol 3.5:3.5:3 | 0.5 | 218 ± 8.5 | 0.27 ± 0.02 | −12.4 ± 0.4 | - |
S14 | Tw60:Sp60:Chol 3.5:3.5:3 | 1 | 234 ± 5.7 | 0.31 ± 0.06 | −11.3 ± 1.5 | - |
S15 | Tw60:Sp60:Chol 3.5:3.5:3 | 2.5 | 240 ± 7.6 | 0.27 ± 0.02 | −10.1 ± 1.7 | - |
S16 | Tw60:Sp60:Chol 3.5:3.5:3 | 2.5 | 235 ± 5.6 | 0.36 ± 0.02 | −11.1 ± 1.7 | 94.1 ± 2.8 |
Niosomes modified with 4F-3K | ||||||
S17 | Tw60:Sp60:Chol 3.5:3.5:3 | 0.5 | 234 ± 8.5 | 0.41 ± 0.04 | −10.2 ± 0.2 | - |
S18 | Tw60:Sp60:Chol 3.5:3.5:3 | 1 | 223 ± 5.7 | 0.31 ± 0.05 | −9.6 ± 0.1 | - |
S19 | Tw60:Sp60:Chol 3.5:3.5:3 | 2.5 | 243 ± 7.6 | 0.36 ± 0.03 | −9.5 ± 0.4 | - |
S20 | Tw60:Sp60:Chol 3.5:3.5:3 | 2.5 | 238 ± 9.6 | 0.40 ± 0.05 | −8.2 ± 0.3 | 90.1 ± 2.3 |
Kinetic Model | Zero Order | First Order | Higuchi | Korsmeyer–Peppas | ||||||
---|---|---|---|---|---|---|---|---|---|---|
R2 | Ko (mg/mL)/h | R2 | KF (h−1) | R2 | KH (mg/mL)/h0.5 | R2 | KKP (h−n) | n | t1/2 (h) | |
Tw60:Sp60:Chol non-modified niosomes (in PBS) | 0.742 | 0.686 | 0.897 | −0.0089 | 0.718 | 7.174 | 0.983 | 12.56 | 0.313 | 82.204 |
Tw60:Sp60:Chol non-modified niosomes (in PBS+ 20 albumin) | 0.813 | 0.634 | 0.914 | −0.008 | 0.712 | 7.01 | 0.989 | 17.61 | 0.23 | 81.58 |
Tw60:Sp60:Chol:3F-3K (in PBS) | 0.540 | 0.657 | 0.873 | −0.0066 | 0.594 | 6.001 | 0.985 | 11.24 | 0.290 | 171.6 |
Tw60:Sp60:Chol:3F-3K (in PBS + 20% albumin) | 0.595 | 0.680 | 0.900 | −0.0072 | 0.596 | 6.542 | 0.982 | 12.25 | 0.290 | 127.7 |
Sample | Size (nm) | PDI | ζ-Potential (mV) | EE (%) | |
---|---|---|---|---|---|
(S5) | Initial | 150 ± 1.1 | 0.35 ± 0.07 | −10.3 ± 1.6 | 92.2 ± 2.1 |
After 1 month storage | 132 ± 2.8 | 0.41 ± 0.09 | −10.6 ± 2.1 | 90.5 ± 4.1 | |
(S16) | Initial | 235 ± 5.6 | 0.36 ± 0.02 | −11.1 ± 1.7 | 94.1 ± 2.8 |
After 1 month storage | 228 ±2.2 | 0.39 ± 0.05 | −11.8 ± 1.2 | 93.8 ± 1.9 |
IC50 (μM ± SD) in Terms of CBD Concentration | |||
---|---|---|---|
Cell Line Sample | T-24 | MJ | HUT-78 |
CBD (as solution) | 12.2 ± 2.1 | 58.6 ± 5.9 | 30.1 ± 5.9 |
Tw60:Sp60:Ch:3F-3K * (S16) | 32.1 ± 6.3 | 74.5 ± 4.4 | 63.9 ± 1.8 |
Tw60:Sp60:Ch:4F-3K * (S20) | 37.3 ± 5.2 | 74.2 ± 3.8 | 64.6 ± 3.7 |
Tw60:Sp60:Ch (N.M.) (S5) | 58.9 ± 6.5 | 69.1 ± 6.2 | 86.2 ± 3.1 |
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Gugleva, V.; Ahchiyska, K.; Georgieva, D.; Mihaylova, R.; Konstantinov, S.; Dimitrov, E.; Toncheva-Moncheva, N.; Rangelov, S.; Forys, A.; Trzebicka, B.; et al. Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes. Pharmaceutics 2023, 15, 2414. https://doi.org/10.3390/pharmaceutics15102414
Gugleva V, Ahchiyska K, Georgieva D, Mihaylova R, Konstantinov S, Dimitrov E, Toncheva-Moncheva N, Rangelov S, Forys A, Trzebicka B, et al. Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes. Pharmaceutics. 2023; 15(10):2414. https://doi.org/10.3390/pharmaceutics15102414
Chicago/Turabian StyleGugleva, Viliana, Katerina Ahchiyska, Dilyana Georgieva, Rositsa Mihaylova, Spiro Konstantinov, Erik Dimitrov, Natalia Toncheva-Moncheva, Stanislav Rangelov, Aleksander Forys, Barbara Trzebicka, and et al. 2023. "Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes" Pharmaceutics 15, no. 10: 2414. https://doi.org/10.3390/pharmaceutics15102414
APA StyleGugleva, V., Ahchiyska, K., Georgieva, D., Mihaylova, R., Konstantinov, S., Dimitrov, E., Toncheva-Moncheva, N., Rangelov, S., Forys, A., Trzebicka, B., & Momekova, D. (2023). Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes. Pharmaceutics, 15(10), 2414. https://doi.org/10.3390/pharmaceutics15102414