Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Solubility Enhancement and Antioxidation Maintenance of CBD Encapsulated in the P407-RUB Nano-micelle System

Author(s): Yan-Ting Su and Jian Zhang*

Volume 21, Issue 2, 2024

Published on: 20 April, 2023

Page: [271 - 282] Pages: 12

DOI: 10.2174/1567201820666230330090025

Price: $65

Abstract

Aim: The aim of this study is to improve the water solubility and stability of cannabidiol (CBD) utilizing micelle technology.

Materials and Methods: Mixing of rubusoside (RUB) with Poloxamer 407 (P407) was explored as the wall material for the preparation of CBD micelles. In this study, CBD-loaded mixed micelles (CBD-M) composed of P407 and RUB was successfully formed by self-assembly then solid were prepared by solvent evaporation. The saturated solubility of CBD-loaded micelles in water increased to 15.60 mg/mL, 1560-fold compared with its intrinsic solubility (0.01 mg/mL). The average size of CBD-M was 103 ± 2.66 nm and the encapsulation efficiency for CBD was 92.8 + 4.7 %, and 18.6 + 0.94% for drug-loading.

Results: The morphology and encapsulation of CBD-M were characterized by TEM, FI-IR, DSC and TG. The CBD-M solution was stable and CBD-M did not precipitate or leak after being diluted and centrifugated. Besides, CBD-M solution was stable for 6 months at 4°C and room temperature. In vitro antioxidant studies found that the antioxidant activity of CBD remained at the same level after micellization.

Conclusion: These results suggest that CBD-M may be a promising and competitive formulation for the delivery of CBD, laying a foundation for improving the bioavailability in the future.

« Previous Next »
Graphical Abstract

[1]
Samanta, D. Cannabidiol: A review of clinical efficacy and safety in epilepsy. Pediatr. Neurol., 2019, 96, 24-29.
[http://dx.doi.org/10.1016/j.pediatrneurol.2019.03.014] [PMID: 31053391]
[2]
Blessing, E.M.; Steenkamp, M.M.; Manzanares, J.; Marmar, C.R. Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics, 2015, 12(4), 825-836.
[http://dx.doi.org/10.1007/s13311-015-0387-1] [PMID: 26341731]
[3]
Mandolini, G.M.; Lazzaretti, M.; Pigoni, A.; Oldani, L.; Delvecchio, G.; Brambilla, P. Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview. Epidemiol. Psychiatr. Sci., 2018, 27(4), 327-335.
[http://dx.doi.org/10.1017/S2045796018000239] [PMID: 29789034]
[4]
Urits, I.; Gress, K.; Charipova, K.; Habib, K.; Lee, D.; Lee, C.; Jung, J.W.; Kassem, H.; Cornett, E.; Paladini, A.; Varrassi, G.; Kaye, A.D.; Viswanath, O. Use of cannabidiol (CBD) for the treatment of chronic pain. Baillieres. Best Pract. Res. Clin. Anaesthesiol., 2020, 34(3), 463-477.
[http://dx.doi.org/10.1016/j.bpa.2020.06.004] [PMID: 33004159]
[5]
Stott, C.G.; White, L.; Wright, S.; Wilbraham, D.; Guy, G.W. A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray. Eur. J. Clin. Pharmacol., 2013, 69(5), 1135-1147.
[http://dx.doi.org/10.1007/s00228-012-1441-0] [PMID: 23179176]
[6]
Scuderi, C.; Filippis, D.D.; Iuvone, T.; Blasio, A.; Steardo, A.; Esposito, G. Cannabidiol in medicine: a review of its therapeutic potential in CNS disorders. Phytother. Res., 2009, 23(5), 597-602.
[http://dx.doi.org/10.1002/ptr.2625] [PMID: 18844286]
[7]
Heussler, H.; Cohen, J.; Silove, N.; Tich, N.; Bonn-Miller, M.O.; Du, W.; O’Neill, C.; Sebree, T. A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome. J. Neurodev. Disord., 2019, 11(1), 16.
[http://dx.doi.org/10.1186/s11689-019-9277-x] [PMID: 31370779]
[8]
dos-Santos-Pereira, M.; Guimarães, F.S.; Del-Bel, E.; Raisman-Vozari, R.; Michel, P.P. Cannabidiol prevents LPS‐induced microglial inflammation by inhibiting ROS/NF‐κB‐dependent signaling and glucose consumption. Glia, 2020, 68(3), 561-573.
[http://dx.doi.org/10.1002/glia.23738] [PMID: 31647138]
[9]
Atalay, S.; Jarocka-Karpowicz, I.; Skrzydlewska, E. Antioxidative and anti-inflammatory properties of cannabidiol. Antioxidants, 2019, 9(1), 21.
[http://dx.doi.org/10.3390/antiox9010021] [PMID: 31881765]
[10]
Borges, R.S.; da Silva, A.B.F. Cannabidiol as an Antioxidant. In: Handbook of Cannabis and Related Pathologies; , 2017; p. 122-130.
[11]
Massi, P.; Solinas, M.; Cinquina, V.; Parolaro, D. Cannabidiol as potential anticancer drug. Br. J. Clin. Pharmacol., 2013, 75(2), 303-312.
[http://dx.doi.org/10.1111/j.1365-2125.2012.04298.x] [PMID: 22506672]
[12]
Bergamaschi, M.M.; Queiroz, R.H.; Zuardi, A.W.; Crippa, J.A. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr. Drug Saf., 2011, 6(4), 237-249.
[http://dx.doi.org/10.2174/157488611798280924] [PMID: 22129319]
[13]
Millar, S.A.; Stone, N.L.; Yates, A.S.; O’Sullivan, S.E. A systematic review on the pharmacokinetics of cannabidiol in humans. Front. Pharmacol., 2018, 9, 1365.
[http://dx.doi.org/10.3389/fphar.2018.01365] [PMID: 30534073]
[14]
Hernán Pérez de la Ossa, D.; Ligresti, A.; Gil-Alegre, M.E.; Aberturas, M.R.; Molpeceres, J.; Di Marzo, V.; Torres Suárez, A.I. Poly-ε-caprolactone microspheres as a drug delivery system for cannabinoid administration: Development, characterization and in vitro evaluation of their antitumoral efficacy. J. Control. Release, 2012, 161(3), 927-932.
[http://dx.doi.org/10.1016/j.jconrel.2012.05.003] [PMID: 22580111]
[15]
Jason, W.; Dilkushi, P.; Stephanie, K. Cannabidiol: Pre-review repotrt of expert committee on drug dependence thirty-ninth meeting. World Health Organization. Cannabidiol (CBD) pre-review report agenda item 5.2[C]. Expert Committee on Drug Dependence Thirty-ninth Meeting. 2017.
[16]
Kawabata, Y.; Wada, K.; Nakatani, M.; Yamada, S.; Onoue, S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications. Int. J. Pharm., 2011, 420(1), 1-10.
[http://dx.doi.org/10.1016/j.ijpharm.2011.08.032] [PMID: 21884771]
[17]
Scully, C. Cannabis; adverse effects from an oromucosal spray. Br. Dent. J., 2007, 203(6), E12.
[http://dx.doi.org/10.1038/bdj.2007.749] [PMID: 17703180]
[18]
Knaub, K.; Sartorius, T.; Dharsono, T.; Wacker, R.; Wilhelm, M.; Schön, C. A novel Self-Emulsifying Drug Delivery System (SEDDS) Based on VESIsorb® formulation technology improving the oral bioavailability of cannabidiol in healthy subjects. Molecules, 2019, 24(16), 2967.
[http://dx.doi.org/10.3390/molecules24162967] [PMID: 31426272]
[19]
Nakano, Y.; Tajima, M.; Sugiyama, E.; Sato, V.H.; Sato, H. Development of a novel nano¬emulsion formulation to improve intestinal absorption of cannabidiol. Med. Cannabis Cannabinoids, 2019, 2(1), 35-42.
[http://dx.doi.org/10.1159/000497361] [PMID: 34676332]
[20]
Li, H.; Chang, S-L.; Chang, T-R.; You, Y.; Wang, X-D.; Wang, L-W.; Yuan, X-F.; Tan, M-H.; Wang, P-D.; Xu, P-W.; Gao, W-B.; Zhao, Q-S.; Zhao, B. Inclusion complexes of cannabidiol with β-cyclodextrin and its derivative: Physicochemical properties, water solubility, and antioxidant activity. J. Mol. Liq., 2021, 334, 116070.
[http://dx.doi.org/10.1016/j.molliq.2021.116070]
[21]
Mannila, J.; Järvinen, T.; Järvinen, K.; Jarho, P. Precipitation complexation method produces cannabidiol/beta-cyclodextrin inclusion complex suitable for sublingual administration of cannabidiol. J. Pharm. Sci., 2007, 96(2), 312-319.
[http://dx.doi.org/10.1002/jps.20766] [PMID: 17051591]
[22]
Koch, N.; Jennotte, O.; Gasparrini, Y.; Vandenbroucke, F.; Lechanteur, A.; Evrard, B. Cannabidiol aqueous solubility enhancement: Comparison of three amorphous formulations strategies using different type of polymers. Int. J. Pharm., 2020, 589, 119812.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119812] [PMID: 32882367]
[23]
Bose, A.; Roy Burman, D.; Sikdar, B.; Patra, P. Nanomicelles: Types, properties and applications in drug delivery. IET Nanobiotechnol., 2021, 15(1), 19-27.
[http://dx.doi.org/10.1049/nbt2.12018] [PMID: 34694727]
[24]
Sayed, S.; Elsayed, I.; Ismail, M.M. Optimization of β-cyclodextrin consolidated micellar dispersion for promoting the transcorneal permeation of a practically insoluble drug. Int. J. Pharm., 2018, 549(1-2), 249-260.
[http://dx.doi.org/10.1016/j.ijpharm.2018.08.001] [PMID: 30077759]
[25]
Zhang, H.; Yang, X.; Zhao, L.; Jiao, Y.; Liu, J.; Zhai, G. In vitro and in vivo study of Baicalin-loaded mixed micelles for oral delivery. Drug Deliv., 2016, 23(6), 1933-1939.
[PMID: 25693642]
[26]
Liu, Z.; Zhang, F.; Koh, G.Y.; Dong, X.; Hollingsworth, J.; Zhang, J.; Russo, P.S.; Yang, P.; Stout, R.W. Cytotoxic and antiangiogenic paclitaxel solubilized and permeation-enhanced by natural product nanoparticles. Anticancer Drugs, 2015, 26(2), 167-179.
[http://dx.doi.org/10.1097/CAD.0000000000000173] [PMID: 25243454]
[27]
Zhang, F.; Koh, G.Y.; Jeansonne, D.P.; Hollingsworth, J.; Russo, P.S.; Vicente, G.; Stout, R.W.; Liu, Z. A novel solubility-enhanced curcumin formulation showing stability and maintenance of anticancer activity. J. Pharm. Sci., 2011, 100(7), 2778-2789.
[http://dx.doi.org/10.1002/jps.22512] [PMID: 21312196]
[28]
Zhang, F.; Koh, G.Y.; Hollingsworth, J.; Russo, P.S.; Stout, R.W.; Liu, Z. Reformulation of etoposide with solubility-enhancing rubusoside. Int. J. Pharm., 2012, 434(1-2), 453-459.
[http://dx.doi.org/10.1016/j.ijpharm.2012.06.013] [PMID: 22698860]
[29]
Zhang, J.; Chou, G.; Liu, Z.; Liu, M. Employing rubusoside to improve the solubility and permeability of antitumor compound betulonic acid. Nanomedicine (Lond.), 2016, 11(21), nnm-2016-0188.
[http://dx.doi.org/10.2217/nnm-2016-0188] [PMID: 27759492]
[30]
Song, K.; Xin, M.; Yu, H.; Zheng, Z.; Li, J.; Li, M.; Guo, H.; Tan, Y.; Wu, X. Novel ultra-small micelles based on rebaudioside A: A potential nanoplatform for ocular drug delivery. Int. J. Pharm., 2018, 552(1-2), 265-276.
[http://dx.doi.org/10.1016/j.ijpharm.2018.10.006] [PMID: 30291959]
[31]
Pitto-Barry, A.; Barry, N.P.E. Pluronic® block-copolymers in medicine: from chemical and biological versatility to rationalisation and clinical advances. Polym. Chem., 2014, 5(10), 3291-3297.
[http://dx.doi.org/10.1039/C4PY00039K]
[32]
Ćirin, D.; Krstonošić, V.; Sazdanić, D. Synergism and antagonism in mixed monolayers: Brij S20/poloxamer 407 and Triton X-100/poloxamer 407 mixtures. Fluid Phase Equilib., 2018, 473, 220-225.
[http://dx.doi.org/10.1016/j.fluid.2018.06.009]
[33]
Ćirin, D.; Krstonošić, V.; Poša, M. Properties of poloxamer 407 and polysorbate mixed micelles: Influence of polysorbate hydrophobic chain. J. Ind. Eng. Chem., 2017, 47, 194-201.
[http://dx.doi.org/10.1016/j.jiec.2016.11.032]
[34]
Liu, X.; Chen, Y.; Chen, X.; Su, J.; Huang, C. Enhanced efficacy of baicalin-loaded TPGS polymeric micelles against periodontitis. Mater. Sci. Eng. C, 2019, 101, 387-395.
[http://dx.doi.org/10.1016/j.msec.2019.03.103] [PMID: 31029332]
[35]
Tura, M.; Mandrioli, M.; Gallina Toschi, T. Preliminary Study: Comparison of Antioxidant Activity of Cannabidiol (CBD) and α-Tocopherol Added to Refined Olive and Sunflower Oils. Molecules, 2019, 24(19), 3485.
[http://dx.doi.org/10.3390/molecules24193485] [PMID: 31561446]
[36]
Coulombier, N.; Nicolau, E.; Le Déan, L.; Antheaume, C.; Jauffrais, T.; Lebouvier, N. Impact of light intensity on antioxidant activity of tropical microalgae. Mar. Drugs, 2020, 18(2), 122.
[http://dx.doi.org/10.3390/md18020122] [PMID: 32085557]
[37]
Francke, N.M.; Schneider, F.; Baumann, K.; Bunjes, H. Formulation of cannabidiol in colloidal lipid carriers. Molecules, 2021, 26(5), 1469.
[http://dx.doi.org/10.3390/molecules26051469] [PMID: 33800445]
[38]
Pu, H.; Sun, Q.; Tang, P.; Zhao, L.; Li, Q.; Liu, Y.; Li, H. Characterization and antioxidant activity of the complexes of tertiary butylhydroquinone with β-cyclodextrin and its derivatives. Food Chem., 2018, 260, 183-192.
[http://dx.doi.org/10.1016/j.foodchem.2018.04.008] [PMID: 29699660]
[39]
Chen, J.; Khiste, S.K.; Fu, X.; Roy, K.R.; Dong, Y.; Zhang, J.; Liu, M.; Liu, Y.Y.; Liu, Z. Rubusoside-assisted solubilization of poorly soluble C6-Ceramide for a pilot pharmacokinetic study. Prostagland. Other Lipid Mediat., 2020, 146, 106402.
[http://dx.doi.org/10.1016/j.prostaglandins.2019.106402] [PMID: 31841664]
[40]
Zhang, W.; Li, C.; Jin, Y.; Liu, X.; Wang, Z.; Shaw, J.P.; Baguley, B.C.; Wu, Z.; Liu, J. Multiseed liposomal drug delivery system using micelle gradient as driving force to improve amphiphilic drug retention and its anti-tumor efficacy. Drug Deliv., 2018, 25(1), 611-622.
[http://dx.doi.org/10.1080/10717544.2018.1440669] [PMID: 29493300]
[41]
Grimaudo, M.A.; Pescina, S.; Padula, C.; Santi, P.; Concheiro, A.; Alvarez-Lorenzo, C.; Nicoli, S. Poloxamer 407/TPGS mixed micelles as promising carriers for cyclosporine ocular delivery. Mol. Pharm., 2018, 15(2), 571-584.
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00939] [PMID: 29313693]
[42]
Zhao, L.; Du, J.; Duan, Y.; Zang, Y.; Zhang, H.; Yang, C.; Cao, F.; Zhai, G. Curcumin loaded mixed micelles composed of Pluronic P123 and F68: Preparation, optimization and in vitro characterization. Colloids Surf. B Biointerfaces, 2012, 97, 101-108.
[http://dx.doi.org/10.1016/j.colsurfb.2012.04.017] [PMID: 22609589]
[43]
Raval, A.; Parmar, A.; Raval, A.; Bahadur, P. Preparation and optimization of media using Pluronic® micelles for solubilization of sirolimus and release from the drug eluting stents. Colloids Surf. B Biointerfaces, 2012, 93, 180-187.
[http://dx.doi.org/10.1016/j.colsurfb.2011.12.034] [PMID: 22265756]
[44]
Lv, P.; Zhang, D.; Guo, M.; Liu, J.; Chen, X.; Guo, R.; Xu, Y.; Zhang, Q.; Liu, Y.; Guo, H.; Yang, M. Structural analysis and cytotoxicity of host-guest inclusion complexes of cannabidiol with three native cyclodextrins. J. Drug Deliv. Sci. Technol., 2019, 51, 337-344.
[http://dx.doi.org/10.1016/j.jddst.2019.03.015]
[45]
Gulcin, İ. Antioxidants and antioxidant methods: An updated overview. Arch. Toxicol., 2020, 94(3), 651-715.
[http://dx.doi.org/10.1007/s00204-020-02689-3] [PMID: 32180036]
[46]
Volmajer Valh, J.; Peršin, Z. Vončina, B.; Vrezner, K.; Tušek, L.; Fras Zemljič L. Microencapsulation of cannabidiol in liposomes as coating for cellulose for potential advanced sanitary material. Coatings, 2020, 11(1), 3.
[http://dx.doi.org/10.3390/coatings11010003]
[47]
Hacke, A.C.M.; Lima, D.; de Costa, F.; Deshmukh, K.; Li, N.; Chow, A.M.; Marques, J.A.; Pereira, R.P.; Kerman, K. Probing the antioxidant activity of Δ 9 -tetrahydrocannabinol and cannabidiol in Cannabis sativa extracts. Analyst (Lond.), 2019, 144(16), 4952-4961.
[http://dx.doi.org/10.1039/C9AN00890J] [PMID: 31318364]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy