Experimental acute anti-inflammatory activity of preparations with complexed cannabidiol in carriers
DOI:
https://doi.org/10.1590/s2175-97902023e221000Keywords:
Cannabidiol;, Beta cyclodextrin;, Activated charcoal;, Anti-inflammatory activityAbstract
Cannabidiol (CBD) is a bioactive compound with promising anti-inflammatory results but has low aqueous solubility. Complexation of drugs with this characteristic in carriers is an alternative to improve their efficiency. This study aimed to prepare and characterize CBD complexes in different carriers, and to evaluate the anti-inflammatory effect of such preparations using an experimental model of edema induction in rat paws. The results were compared to a reference drug, ibuprofen (IBU). The carriers evaluated were beta cyclodextrin (bCD) and activated charcoal (AC). Quantification of the drugs in the complexes was determined, and different qualitative analyses were also performed. Oral treatments in single doses with CBD showed inhibitory effects similar to that of IBU, potentiating its bioactivity without significant adverse effects. CBD*bCD doses at 4.375, 8.75, 17.5, and 35 mg/kg significantly reduced the intensity of edema compared to equivalent doses of pure bioactive. In contrast, CBD*AC did not generate benefits. There was no significant inhibitory effect on myeloperoxidase activity, requiring more specific analyses to assess this parameter. The results suggest that the CBD*bCD complexation is perfectly feasible, increasing its anti-edematogenic efficacy in the experimental model used.
Downloads
References
Abarca RL, Rodríguez FJ, Guarda A, Galotto MJ, Bruna JE. Characterization of beta-cyclodextrin inclusion complexes containing an essential oil component. Food Chem. 2016;196:968-75.
Abotsi WKM, Lamptey SB, Afrane S, Boakye-Gyasi E, Umoh RU, Woode E. An evaluation of the anti-inflammatory, antipyretic and analgesic effects of hydroethanol leaf extract of Albizia zygia in animal models. Pharm Biol. 2017;55(1):338-48.
Almeida M, Rocha BA, Francisco CRL, Miranda CG, Santos PDD, de Araujo PHH, et al. Evaluation of the in vivo acute antiinflammatory response of curcumin-loaded nanoparticles. Food Funct. 2018;9(1):440-9.
Angelova V, Ivanova R, Delibaltova V, Ivanov K. Bio-accumulation and distribution of heavy metals in fibre crops (flax, cotton and hemp). Ind Crops Prod. 2004;19(3):197-205.
Assadpour E, Rezaei A, Das SS, Rao BVK, Singh SK, Kharazmi MS, et al. Cannabidiol-Loaded Nanocarriers and Their Therapeutic Applications. Pharm. 2023;16(4):487.
ASTM. Standard terminology relating to textiles (d123-00b). American Society for Testing and Materials. 2003
ASTM. Standard test method for chemical analysis of wood charcoal. Designation: D1762 - 84 (reapproved). American Society for Testing and Materials. 2007
Branca C, Di Blasi C, Galgano A. Experimental analysis about the exploitation of industrial hemp (Cannabis sativa) in pyrolysis. Fuel Process Technol. 2017;162:20-9.
Brazil. Sistema Harmonizado de Designação e de Codificação de Mercadorias. Secretaria da Fazenda. Diário Oficial da União 18 jan 2008; Suplemento - Seção 1.
Cayman. Cannabidiol (item nº 90081). Product information [Internet]. 2015 [cited 2023 Jan 19]. Available from: Available from: https://www.caymanchem.com/pdfs/90081.pdf
» https://www.caymanchem.com/pdfs/90081.pdf
Cayman. (±)-ibuprofen (item nº 70280). Product information [Internet]. 2017 [cited 2023 Jan 19]. Available from: Available from: https://www.caymanchem.com/pdfs/70280.pdf
» https://www.caymanchem.com/pdfs/70280.pdf
Chandra S, Lata H, ElSohly MA. Cannabis sativa L. - Botany and biotechnology. 1st ed. Springer Cham; 2017.
Costa B, Colleoni M, Conti S, Parolaro D, Franke C, Trovato AE, et al. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn Schmiedebergs Arch Pharmacol. 2004;369(3):294-9.
Costa B, Trovato AE, Comelli F, Giagnoni G, Colleoni M. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharmacol. 2007;556:75-83.
Dizbay-Onat M, Vaidya UK, Balanay JAG, Lungu CT. Preparation and characterization of flax, hemp and sisal fiber-derived mesoporous activated carbon adsorbents. Adsorp Sci Technol. 2018;36(1-2):441-57.
Friuli V, Bruni G, Musitelli G, Conte U, Maggi L. Influence of dissolution media and presence of alcohol on the in vitro performance of pharmaceutical products containing an insoluble drug. J Pharm Sci. 2018;107(1):507-11.
Frömming KH, Szejtli J. Cyclodextrin inclusion complexes. In: Cyclodextrins in pharmacy. Topics in Inclusion Science, vol 5. Springer Dordrecht; 1994:45-82.
Garrett ER, Hunt CA. Physicochemical properties, solubility, and protein-binding of delta-9-tetrahydrocannabinol. J Pharm Sci , 1974;63(7):1056-64.
Garside P, Wyeth P. Identification of cellulosic fibres by ftir spectroscopy: Thread and single fibre analysis by attenuated total reflectance. Stud Conserv. 2003;48(4):269-75.
Gaylord. Simethyl sulfoxide - solubility data. Bulletin 102 [Internet]. 2014 [cited 2023 Jan 19]. Available from: Available from: https://www.gaylordchemical.com/content/uploads/2020/08/GC-Literature-102B-ENG-Low.pdf
» https://www.gaylordchemical.com/content/uploads/2020/08/GC-Literature-102B-ENG-Low.pdf
Hossain MZ, Wu W, Xu WZ, Chowdhury MBI, Jhawar AK, Machin D, et al. High-surface-area mesoporous activated carbon from hemp bast fiber using hydrothermal processing. C. 2018;4(3):38-52.
Inácio FD, Ferreira RO, Araujo CAV, Peralta RM, Souza CGM. Production of enzymes and biotransformation of orange waste by oyster mushroom, Pleurotus pulmonarius (fr.) quél. Adv Appl Microbiol. 2015;5(1):1-8.
Juurlink DN. Activated charcoal for acute overdose: A reappraisal. Br J Clin Pharmacol. 2016;81(3):482-7.
Khan MA, Wajid A, Noor S, Khattak DK, Akhter S, Rahman Iu. Effect of soil contamination on some heavy metals content of Cannabis sativa J Chem Soc Pak. 2008;30(6):805-9.
Linger P, Müssig J, Fischer H, Kobert J. Industrial hemp (Cannabis sativa l.) growing on heavy metal contaminated soil: Fibre quality and phytoremediation potential. Ind Crops Prod . 2002;16(1):33-42.
Lin-Vien D, Colthup NB, Fateley WG, Grasselli JG. The handbook of infrared and raman characteristic frequencies of organic molecules. 1st ed. Academic Press; 1991.
Lv P, Zhang D, Guo M, Liu J, Chen X, Guo R, et al. Structural analysis and cytotoxicity of host-guest inclusion complexes of cannabidiol with three native cyclodextrins. J Drug Deliv Sci Technol. 2019;51:337-44.
Mannila J, Järvinen T, Järvinen K, Jarho P. Precipitation complexation method produces cannabidiol/β-cyclodextrin inclusion complex suitable for sublingual administration of cannabidiol. J Pharm Sci . 2007;96(2):312-9.
Marrot L, Candelier K, Valette J, Lanvin C, Horvat B, Legan L, et al. Valorization of hemp stalk waste through thermochemical conversion for energy and electrical applications. Waste Biomass Valorization. 2021;13:2267-85.
Miriyala N, Ouyang DF, Perrie Y, Lowry D, Kirby DJ. Activated carbon as a carrier for amorphous drug delivery: Effect of drug characteristics and carrier wettability. European Eur J Pharm Biopharm. 2017;115:197-205.
Morin-Crini N, Loiacono S, Placet V, Torri G, Bradu C, Kostić M, et al. Hemp-based materials for metal removal. In: Green adsorbents for pollutant removal: Innovative materials. Springer International Publishing; 2018:1-34.
Pejic BM, Kostic MM, Skundric PD, Praskalo JZ. The effects of hemicelluloses and lignin removal on water uptake behavior of hemp fibers. Bioresour Technol. 2008;99(15):7152-9.
Shoyama Y, Morimoto S, Nishioka I. Cannabis. XV. Preparation and stability of δ9-tetrahydrocannabinol-b-cyclodextrin inclusion complex. J Nat Prod, 1983;46(5):633-7.
Sing KSW, Everett DH, Haul RAW, Moscou L, Pierotti RA, Rouquerol J, et al. Reporting physisorption data for gas solid systems with special reference to the determination of surface-area and porosity (recommendations 1984). Pure Appl Chem. 1985;57(4):603-19.
Siwulski M, Drzewiecka K, Sobieralski K, Chong Y. Comparison of growth and enzymatic activity of mycelium and yielding of pleurotus ostreatus (fr.) kumm. On different substrates. Acta Sci Pol-Hortoru. 2010;9(3):45-50.
Strzepa A, Pritchard KA, Dittel BN. Myeloperoxidase: A new player in autoimmunity. Cell Immunol. 2017;317:1-8.
SWGDRUG. Monographs: Marijuana. Scientific working group for the analysis of seized drugs [Internet]. 2005 [cited 2023 Jan 19]. Available from: Available from: http://www.swgdrug.org/monographs/marijuana.pdf
» http://www.swgdrug.org/monographs/marijuana.pdf
Thongpat W, Taweekun J, Maliwan K. Synthesis and characterization of microporous activated carbon from rubberwood by chemical activation with KOH. Carbon Lett. 2021;31(5):1079-88.
UNODC. Commission on Narcotic Drugs, 63nd session: Decision 63/14 (cannabis and cannabis-related substances). United Nations Office on Drugs and Crime [Internet]. 2020 [cited 2023 May 1]. Available from: Available from: https://www.unodc.org/documents/commissions/CND/Drug_Resolutions/2020-2029/2020/Decision_63_14.pdf
» https://www.unodc.org/documents/commissions/CND/Drug_Resolutions/2020-2029/2020/Decision_63_14.pdf
USA. Public law 115-334. Agriculture improvement Act of 2018. United States of America [Internet]. 2018 [cited 2023 Jan 19]. Available from: Available from: https://www.congress.gov/115/plaws/publ334/PLAW-115publ334.pdf
» https://www.congress.gov/115/plaws/publ334/PLAW-115publ334.pdf
Vlad R-A, Sovány T, Kristó K, Ibrahim YH-EY, Ciurba A, Aigner Z, et al. Structural and thermal analysis of cannabidiol orodispersible formulations. Farmacia, 2021;69(3):426-33.
Wang P, Ye H, Yin YX, Chen H, Bian YB, Wang ZR, et al. Fungi-enabled synthesis of ultrahigh-surface-area porous carbon. Adv Mater. 2019;31(4).
Wang XM, Xu LJ, Xu JH, Zhang GZ, Wu SB Preparation and capability of activated carbons with high specific surface area by microbial enzymatic and chemical activation. Trans Tech Publications. 2011;236-8:225-8.
WHO. Fortieth meeting of the expert committee on drug dependence, 40th ECDD. World Health Organization [Internet]. 2018 [cited 2023 May 1]. Available from: Available from: https://apps.who.int/iris/bitstream/handle/10665/279948/9789241210225-eng.pdf
» https://apps.who.int/iris/bitstream/handle/10665/279948/9789241210225-eng.pdf
Wisniewski-Rebecca ES, Rocha BA, Wiirzler LAM, Cuman RKN, Velazquez-Martinez CA, Bersani-Amado CA. Synergistic effects of anethole and ibuprofen in acute inflammatory response. Chem Biol Interact. 2015;242:247-53.
Wittkowski KM. Use of cyclodextrins to reduce endocytosis in malignant and neurodegenerative disorders. Patent No. WO2017163128A2. 2017.
Yaneva ZL. Nonsteroidal anti-inflammatory drug solid-state microencapsulation on green activated carbon - mass transfer and host-guest interactions. Chem Biochem Eng Q. 2019;33(2):249-69.
Yang H, Yan R, Chen H, Lee DH, Zheng C. Characteristics of hemicellulose, cellulose and lignin pyrolysis. Fuel. 2007;86(12):1781-8.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Brazilian Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on-line journal has open and free access.
