Current trends on cannabidiol delivery systems: where are we and where are we going?

References

• Mechoulam R, Peters M, Murillo-Rodriguez E, et al. Cannabidiol – recent advances. Chem Biodivers. 2007;4(8):1678–1692.
   PubMed Web of Science ®Google Scholar
• Pisanti S, Malfitano AM, Ciaglia E, et al. Cannabidiol: state of the art and new challenges for therapeutic applications. Pharmacol Ther. 2017;175(2017):133–150.
   PubMedGoogle Scholar
• Britch S, Babalonis S, Walsh S. Cannabidiol: pharmacology and therapeutic targets. Psychopharmacology (Berl). 2021;238(1):9–28. .
   PubMed Web of Science ®Google Scholar
• Millar SA, Stone NL, Yates AS, et al. A systematic review on the pharmacokinetics of cannabidiol in humans. Front Pharmacol. 2018;9(2018):1365.
   PubMedGoogle Scholar
• Mechoulam R, Hanuš L. Cannabidiol: an overview of some chemical and pharmacological aspects. Part I: chemical aspects. Chem Phys Lipids. 2002;121(1):35–43.
   PubMed Web of Science ®Google Scholar
• Franco V, Gershkovich P, Perucca E, et al. The interplay between liver first pass effect and lymphatic absorption of cannabidiol and its implications for cannabidiol oral formulations. Clin Pharmacokinet. 2020;59:1493–1500. .
   PubMed Web of Science ®Google Scholar
• Perucca E, Bialer M. Critical aspects affecting cannabidiol oral bioavailability and metabolic elimination, and related clinical implications. CNS Drugs. 2020;34:795–800.
   PubMed Web of Science ®Google Scholar
• Wu C, Benet L. Predicting drug disposition via application of BCS: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 2005;22(1):11–23.
   PubMed Web of Science ®Google Scholar
• Amidon G, Lennernas H, Shah V, et al. A theoretical basis for biopharmaceutics drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413–420.
   PubMed Web of Science ®Google Scholar
• Alvebratt C, Keemink J, Edueng K, et al. An in vitro dissolution–digestion–permeation assay for the study of advanced drug delivery systems. Eur J Pharm Biopharm. 2020;149:21–29.
   PubMed Web of Science ®Google Scholar
• Sativex Oromucosal Spray: Summary of Product Characteristics. Electronic medicines compendium (emc): GW Pharma Ltd; 2020 [updated 2020 Aug 20; cited 2021 Mar 26]. Available from: https://www.gwpharm.com/healthcare-professionals/sativex
   Google Scholar
• Drug Approval Package: Epidiolex (Cannabidiol). FDA Database: US Food and Drug Administration 2018 [updated 2018 Jul 27; cited 2021 Mar 26]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210365Orig1s000TOC.cfm
   Google Scholar
• Epidyolex (Cannabidiol). EMA website: The European Medicines Agency (EMA); 2019 [updated 2021 Mar 03; cited 2021 Mar 26]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/epidyolex#product-information-section
   Google Scholar
• Geffrey A, Pollack S, Bruno P, et al. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015;56(8):1246–1251.
   PubMed Web of Science ®Google Scholar
• Warren C, Chadha A, Sicherer S, et al. Prevalence and severity of sesame allergy in the United States. JAMA Network Open. 2019;2(8):e199144.
   PubMed Web of Science ®Google Scholar
• Göke K, Lorenz T, Repanas A, et al. Novel strategies for the formulation and processing of poorly water-soluble drugs. Eur J Pharm Biopharm. 2019;126:40–56. .
   Web of Science ®Google Scholar
• Cosco D, Celia C, Cilurzo F, et al. Colloidal carriers for the enhanced delivery through the skin. Expert Opin Drug Deliv. 2008;5(7):737–755.
   PubMed Web of Science ®Google Scholar
• Dubey V, Mishra D, Nahar M, et al. Vesicles as tools for the modulation of skin permeability. Expert Opin Drug Deliv. 2007;4(6):579–593.
   PubMed Web of Science ®Google Scholar
• Senel S, Rathbone MJ, Cansız M, et al. Recent developments in buccal and sublingual delivery systems. Expert Opin Drug Deliv. 2012;9(6):615–628.
   PubMed Web of Science ®Google Scholar
• Laffleur F, Keckeis V. Advances in drug delivery systems: work in progress still needed? Int J Pharm. 2020;2:100050.
   Google Scholar
• Boyd B, Bergström C, Vinarov Z, et al. Successful oral delivery of poorly water-soluble drugs both depends on the intraluminal behavior of drugs and of appropriate advanced drug delivery systems. Eur J Pharm Sci. 2019;137:104967. .
   PubMed Web of Science ®Google Scholar
• Lanza J, Pomel S, Loiseau P, et al. Recent advances in amphotericin B delivery strategies for the treatment of leishmaniases. Expert Opin Drug Deliv. 2019;16(10):1063–1079.
   PubMed Web of Science ®Google Scholar
• Kaiser P, Wächter J, Windbergs M. Therapy of infected wounds: overcoming clinical challenges by advanced drug delivery systems. Drug Deliv Transl Res. 2021. DOI:https://doi.org/10.1007/s13346-021-00932-7
   Google Scholar
• Di Bello MP, Bloise E, Mazzetto SE, et al. Formulation and chemical stability in aqueous media of cannabidiol embedded in cardanol-based nanovesicles. ACS Sustain Chem Eng. 2017;5(10):8870–8875.
   Web of Science ®Google Scholar
• Aparicio-Blanco J, Romero IA, Male DK, et al. Cannabidiol enhances the passage of lipid nanocapsules across the blood–brain barrier both in vitro and in vivo. Mol Pharm. 2019;16(5):1999–2010.
   PubMedGoogle Scholar
• Mu H, Holm R, Mullertz A. Lipid-based formulations for oral administration of poorly water-soluble drugs. Int J Pharm. 2013;453(1):215–224.
   PubMed Web of Science ®Google Scholar
• Naseri N, Valizadeh H, Zakeri-Milani P. Solid lipid nanoparticles and nanostructured lipid carriers: structure, preparation and application. Adv Pharm Bull. 2015;5(3):305–313.
   PubMed Web of Science ®Google Scholar
• Gordillo-Galeano A, Mora-Huertas CE. Solid lipid nanoparticles and nanostructured lipid carriers: a review emphasizing on particle structure and drug release. Eur J Pharm Biopharm. 2018;133(2018):285–308. .
   PubMedGoogle Scholar
• Aparicio-Blanco J, Sebastian V, Benoit JP, et al. Lipid nanocapsules decorated and loaded with cannabidiol as targeted prolonged release carriers for glioma therapy: in vitro screening of critical parameters. Eur J Pharm Biopharm. 2019;134(2019):126–137.
   PubMedGoogle Scholar
• Agrawal M, Saraf S, Saraf S, et al. Recent advancements in the field of nanotechnology for the delivery of anti-Alzheimer drug in the brain region. Expert Opin Drug Deliv. 2018;15(6):589–617. .
   PubMed Web of Science ®Google Scholar
• Saeedi M, Eslamifar M, Khezri K, et al. Applications of nanotechnology in drug delivery to the central nervous system. Biomed Pharmacother. 2019;111(2019):666–675.
   PubMedGoogle Scholar
• Rani S, Rana R, Saraogi GK, et al. Self-emulsifying oral lipid drug delivery systems: advances and challenges. AAPS PharmSciTech. 2019;20(3):129.
   PubMed Web of Science ®Google Scholar
• Cherniakov I, Izgelov D, Domb AJ, et al. The effect of Pro NanoLipospheres (PNL) formulation containing natural absorption enhancers on the oral bioavailability of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a rat model. Eur J Pharm Sci. 2017;109(2017):21–30.
   PubMedGoogle Scholar
• Cherniakov I, Izgelov D, Barasch D, et al. Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration. J Control Release. 2017;266(2017):1–7.
   PubMedGoogle Scholar
• Atsmon J, Cherniakov I, Izgelov D, et al. PTL401,a new formulation based on pro-nano dispersion technology, improves oral cannabinoids bioavailability in healthy volunteers. J Pharm Sci. 2018;107(5):1423–1429.
   PubMed Web of Science ®Google Scholar
• Lin PC, Lin S, Wang PC, et al. Techniques for physicochemical characterization of nanomaterials. Biotechnol Adv. 2014;32(4):711–726. .
   PubMed Web of Science ®Google Scholar
• Shao B, Cui C, Ji H, et al. Enhanced oral bioavailability of piperine by self-emulsifying drug delivery systems: in vitro, in vivo and in situ intestinal permeability studies. Drug Deliv. 2015;22(6):740–747.
   PubMed Web of Science ®Google Scholar
• Atsmon J, Heffetz D, Deutsch L, et al. Single-dose pharmacokinetics of oral cannabidiol following administration of PTL101: a new formulation based on gelatin matrix pellets technology. Clin Pharmacol Drug Dev. 2018;7(7):751–758.
   PubMed Web of Science ®Google Scholar
• Mitelpunkt A, Kramer U, Hausman-Kedem M, et al. The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: a phase II, open-label, single-center study. Epilepsy Behav. 2019;98:233–237.
   PubMed Web of Science ®Google Scholar
• Sonawane RO, Patil SD. Gelatin–κ-carrageenan polyelectrolyte complex hydrogel compositions for the design and development of extended-release pellets. Int J Polym Mater. 2017;66(16):812–823.
   Web of Science ®Google Scholar
• Behalo MS, Bloise E, Carbone L, et al. Cardanol-based green nanovesicles with antioxidant and cytotoxic activities. J Exp Nanosci. 2016;11(16):1274–1284.
   Web of Science ®Google Scholar
• Bloise E, Carbone L, Colafemmina G, et al. First example of a lipophilic porphyrin-cardanol hybrid embedded in a cardanol-based micellar nanodispersion. Molecules. 2012;17(10):12252–12261.
   PubMed Web of Science ®Google Scholar
• Amorati R, Attanasi OA, Favi G, et al. Amphiphilic antioxidants from “cashew nut shell liquid” (CNSL) waste. Org Biomol Chem. 2011;9(5):1352–1355.
   PubMed Web of Science ®Google Scholar
• Lodzki M, Godin B, Rakou L, et al. Cannabidiol—transdermal delivery and anti-inflammatory effect in a murine model. J Control Release. 2003;93(3):377–387.
   PubMed Web of Science ®Google Scholar
• Touitou E, Dayan N, Bergelson L, et al. Ethosomes — novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release. 2000;65(3):403–418.
   PubMed Web of Science ®Google Scholar
• Touitou E, Godin B, Weiss C. Enhanced delivery of drugs into and across the skin by ethosomal carriers. Drug Dev Res. 2000;50(3‐4):406–415.
   Web of Science ®Google Scholar
• Mbah CC, Builders PF, Attama AA. Nanovesicular carriers as alternative drug delivery systems: ethosomes in focus. Expert Opin Drug Deliv. 2014;11(1):45–59.
   PubMed Web of Science ®Google Scholar
• Sanjoy-Kumar D, Soumalya C, Chhandita R, et al. Ethosomes as novel vesicular carrier: an overview of the principle, preparation and its applications. Curr Drug Deliv. 2018;15(6):795–817.
   PubMed Web of Science ®Google Scholar
• Bartner LR, McGrath S, Rao S, et al. Pharmacokinetics of cannabidiol administered by 3 delivery methods at 2 different dosages to healthy dogs. Can J Vet Res. 2018;82(3):178–183.
   PubMed Web of Science ®Google Scholar
• Barreras-Urbina CG, Ramírez-Wong B, López-Ahumada GA, et al. Nano- and micro-particles by nanoprecipitation: possible application in the food and agricultural industries. Int J Food Prop. 2016;19(9):1912–1923.
   Web of Science ®Google Scholar
• Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B. 2010;75(1):1–18.
   PubMed Web of Science ®Google Scholar
• Fraguas-Sanchez AI, Fernandez-Carballido A, Simancas-Herbada R, et al. CBD loaded microparticles as a potential formulation to improve paclitaxel and doxorubicin-based chemotherapy in breast cancer. Int J Pharm. 2020;574(2020):118916.
   PubMedGoogle Scholar
• Ossa DHP, Ligresti A, Gil-Alegre ME, et al. Poly-epsilon-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.
   PubMed Web of Science ®Google Scholar
• Ossa DHP, Lorente M, Gil-Alegre ME, et al. Local delivery of cannabinoid-loaded microparticles inhibits tumor growth in a murine xenograft model of glioblastoma multiforme. PLoS One. 2013;8(1):e54795.
   PubMed Web of Science ®Google Scholar
• Ding D, Zhu Q. Recent advances of PLGA micro/nanoparticles for the delivery of biomacromolecular therapeutics. Mater Sci Eng C Mater Biol Appl. 2018;92(2018):1041–1060.
   PubMedGoogle Scholar
• Siepmann J, Elkharraz K, Siepmann F, et al. How autocatalysis accelerates drug release from PLGA-based microparticles: a quantitative treatment. Biomacromolecules. 2005;6(4):2312–2319.
   PubMed Web of Science ®Google Scholar
• Jansook P, Ogawa N, Loftsson T. Cyclodextrins: structure, physicochemical properties and pharmaceutical applications. Int J Pharm. 2018;535(1–2):272–284.
   PubMed Web of Science ®Google Scholar
• Lv P, Zhang D, Guo M, et al. Structural analysis and cytotoxicity of host-guest inclusion complexes of cannabidiol with three native cyclodextrins. J Drug Deliv Sci Tec. 2019;51(2019):337–344.
   Google Scholar
• Mannila J, Jarvinen T, Jarvinen K, et al. Effects of RM-beta-CD on sublingual bioavailability of Delta9-tetrahydrocannabinol in rabbits. Eur J Pharm Sci. 2005;26(1):71–77.
   PubMed Web of Science ®Google Scholar
• Mannila J, Jarvinen T, Jarvinen K, et al. Precipitation complexation method produces cannabidiol/beta-cyclodextrin inclusion complex suitable for sublingual administration of cannabidiol. J Pharm Sci. 2007;96(2):312–319.
   PubMed Web of Science ®Google Scholar
• Miranda JC, Martins TEA, Veiga F, et al. Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs. Braz J Pharm Sci. 2011;47(4):665–681.
   Web of Science ®Google Scholar
• Guo YG, Pratap-Singh A. Emerging strategies for enhancing buccal and sublingual administration of nutraceuticals and pharamaceuticals. J Drug Deliv Sci Tec. 2019;52(2019):440–451.
   Google Scholar
• Ekladious I, Colson YL, Grinstaff MW. Polymer-drug conjugate therapeutics: advances, insights and prospects. Nat Rev Drug Discov. 2019;18(4):273–294.
   PubMed Web of Science ®Google Scholar
• Harris JM, Bentley MD, Moreadith RW, et al. Tuning drug release from polyoxazoline-drug conjugates. Eur Polym J. 2019;120(2019):1–11.
   Google Scholar
• Zapata-Benabithe Z, Carrasco-Marin F, Vicente J, et al. Carbon xerogel microspheres and monoliths from resorcinol-formaldehyde mixtures with varying dilution ratios: preparation, surface characteristics, and electrochemical double-layer capacitances. Langmuir. 2013;29(20):6166–6173.
   PubMed Web of Science ®Google Scholar
• Cortes FB, Zapata K, Rojano BA, et al. Dual-purpose materials based on carbon xerogel microspheres (CXMS) for delayed release of cannabidiol (cbd) and subsequent aflatoxin removal. Molecules. 2019;24(18):3398.
   Web of Science ®Google Scholar
• Chen H, Khemtong C, Yang X, et al. Nanonization strategies for poorly water-soluble drugs. Drug Discov Today. 2011;16(7–8):354–360.
   PubMed Web of Science ®Google Scholar
• Štukelj R, Benčina M, Fanetti M, et al. Synthesis of stable cannabidiol (CBD) nanoparticles in suspension. Mater Tehnol. 2019;53(4):543–549.
   Web of Science ®Google Scholar
• Amaral-Machado L, Oliveira WN, Moreira-Oliveira SS, et al. Use of natural products in asthma treatment. Evid Based Complement Alternat Med. 2020;1–35. DOI:https://doi.org/10.1155/2020/1021258.
   Google Scholar
• Ibeas-Bih C, Chen T, Nunn AVW, et al. Molecular targets of cannabidiol in neurological disorders. Neurotherapeutics. 2015;12(4):699–730.
   PubMed Web of Science ®Google Scholar
• Morales P, Reggio PH, Jagerovic N. An overview on medicinal chemistry of synthetic and natural derivatives of cannabidiol. Front Pharmacol. 2017;8:422.
   PubMed Web of Science ®Google Scholar
• Dutta S, Mahalanobish S, Saha S, et al. Natural products: an upcoming therapeutic approach to cancer. Food Chem Toxicol. 2019;128:240–255.
   PubMed Web of Science ®Google Scholar
• Tran S, DeGiovanni PJ, Piel B, et al. Cancer nanomedicine: a review of recent success in drug delivery. Clin Transl Med. 2017;6(1):44.
   PubMed Web of Science ®Google Scholar
• Hurd YL. Leading the next CBD wave—safety and efficacy. JAMA Psychiatry. 2020;77(4):341–342.
   PubMed Web of Science ®Google Scholar
• Netea MG, Balkwill F, Chonchol M, et al. A guiding map for inflammation. Nat Immunol. 2017;18(8):826–831.
   PubMed Web of Science ®Google Scholar
• Sochocka M, Diniz BS, Leszek J. Inflammatory response in the CNS: friend or foe? Mol Neurobiol. 2017;54(10):8071–8089.
   PubMed Web of Science ®Google Scholar
• Giacoppo S, Galuppo M, Pollastro F, et al. A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis. Daru. 2015;23(3):48.
   PubMedGoogle Scholar
• Chowdhury A, Kunjiappan S, Panneerselvam T, et al. Nanotechnology and nanocarrier-based approaches on treatment of degenerative diseases. Int Nano Lett. 2017;7(2):91–122.
   Web of Science ®Google Scholar
• Stinchcomb ALB, Golinski SL, Hammel MJ, et al. Use of cannabidiol prodrugs in topical and transdermal administration with microneedles. United States patent US 2011/0052694 A1. 2010 Aug 21.
   Google Scholar
• Luan Y, Li X, Li Z, et al., inventors; Luan Yunpeng, assignee. Cannabidiol and alkaline cyclodextrin inclusion compound and preparation method thereof. China patent CN 109833312 A. 2019 June 4.
   Google Scholar
• Luan Y, Li X, Li Z, et al., inventors; Luan Yunpeng, assignee. Cannabidiol nanoemulsion medicine composition and preparation method thereof. China patent CN 110063937 A. 2019 Apr 30.
   Google Scholar
• Lai H, inventor; BN IP-Consulting LLC Binh-An Nguyen, assignee. Process for producing a nano-cbd microemulsion system. Vietnam patent US20200000724 A1. 2020 Jan 2.
   Google Scholar
• Temtsin-Krayz G, Glozman S, Kazhdan P, inventors; Solubest LTD, assignee. Pharmaceutical compositions for transmucosal delivery. Israel patent WO 2017/072774 Al. 2017 May 17.
   Google Scholar
• Fu B, Kong L, Li Z, et al., inventors; Yunnan Lyuxin Biology Pharmacy Co LTD, assignee. Cannabidiol liposome and preparation technology. China patent CN110251466 A. 2019 Sept 20.
   Google Scholar