One of the most common neurological diseases is epilepsy, which not only negatively affects the quality of people's life but also may lead to life-threatening situations when its symptoms such as seizures cannot be controlled medically. A very serious problem to be overcame is the untreatable form of this disease, which cannot be cured by any currently available medicines. Cannabidiol, which is a natural product obtained from Cannabis Sativa, brings a new hope to people suffering from drug-resistant epilepsy. However, the hydrophobic character of this compound significantly lowers its clinical efficiency. One of the promising methods of this substance bioactivity increase is delivery through the skin tissue. In this article, a new type of advanced transdermal systems based on chitosan and ZnO nanoparticles (NPs) has been developed according to Sustained Development principles. The chemical modification of the biopolymer confirmed by FT-IR method resulted in the preparation of the material with great swelling abilities and appropriate water vapor permeability. Obtained nanoparticles were investigated over their crystalline structure and morphology and their positive impact on drug loading capacity and cannabidiol controlled release was proved. The novel biomaterials were confirmed to have conductive properties and not be cytotoxic to L929 mouse fibroblasts.

Department of Biotechnology and Physical Chemistry Faculty of Chemical Engineering and Technology Cracow University of Technology Warszawska 24 Street 31 155 Cracow Poland

Faculty of Mining and Geology Technical University of Ostrava 70800 Ostrava Czech Republic

Nano Prime sp z o o Metalowców 25 39 200 Dębica Poland

Zobrazit více v PubMed

Krauss G.L., Sperling M.R. Treating patients with medically resistant epilepsy. Neurol. Clin. Pract. 2011;1:14–23. doi: 10.1212/CPJ.0b013e31823d07d1. PubMed DOI PMC

Gaston T.E., Szaflarski M., Hansen B., Bebin E.M., Jerzy P., Szaflarski J.P. Quality of life in adults enrolled in an open-label study of cannabidiol (CBD) for treatment-resistant epilepsy. Epilepsy Behav. 2019;95:10–17. doi: 10.1016/j.yebeh.2019.03.035. PubMed DOI

Thompson D.M., Martin R.C., Grayson L.P., Ampah S.B., Cutter G., Szaflarski J.P., Bebin E.M. Cognitive function and adaptive skills after a one-year trial of cannabidiol (CBD) in a pediatric sample with treatment-resistant epilepsy. Epilepsy Behav. 2020;111:107299. doi: 10.1016/j.yebeh.2020.107299. PubMed DOI

Li H., Liu Y., Tian D., Tian L., Ju X., Qi L., Wang Y., Liang C. Overview of cannabidiol (CBD) and its analogues: Structures, biological activities, and neuroprotective mechanisms in epilepsy and Alzheimer’s disease. Eur. J. Med. Chem. 2020;192:112163. doi: 10.1016/j.ejmech.2020.112163. PubMed DOI

Ladha K.S., Ajrawat P., Yang Y., Clarke H. Understanding the Medical Chemistry of the Cannabis Plant is Critical to Guiding Real World Clinical Evidence. Molecules. 2020;25:4042. doi: 10.3390/molecules25184042. PubMed DOI PMC

García-Gutiérrez M.S., Navarrete F., Gasparyan A., Austrich-Olivares A., Sala F., Manzanares J. Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders. Biomolecules. 2020;10:1575. doi: 10.3390/biom10111575. PubMed DOI PMC

Silvestro S., Schepici G., Bramanti P., Mazzon E. Molecular Targets of Cannabidiol in Experimental Models of Neurological Disease. Molecules. 2020;25:5186. doi: 10.3390/molecules25215186. PubMed DOI PMC

Iffland K., Grotenhermen F. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis Cannabinoid Res. 2017;2:139–154. doi: 10.1089/can.2016.0034. PubMed DOI PMC

Mlost J., Bryk M., Starowicz K. Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action. Int. J. Mol. Sci. 2020;21:8870. doi: 10.3390/ijms21228870. PubMed DOI PMC

Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin. Pharm. 2003;42:327–360. doi: 10.2165/00003088-200342040-00003. PubMed DOI

Paudel K.S., Hammell D.C., Agu R.U., Valiveti S., Stinchcomb A.L. Cannabidiol bioavailability after nasal and transdermal application: Effect of permeation enhancers. Drug Dev. Ind. Pharm. 2010;36:1088–1097. doi: 10.3109/03639041003657295. PubMed DOI

Scuderi C., Filippis D., Iuvone T., Blasio A., Steardo A., Esposito G. Cannabidiol in medicine: A review of its therapeutic potential in CNS disorders. Phytother. Res. 2009;23:597–602. PubMed

Grotenhermen F. Cannabinoids for therapeutic use. Designing systems to increase efficacy and reliability. Am. J. Drug Deliv. 2004;2:229–240. doi: 10.2165/00137696-200402040-00003. DOI

Devinsky O., Cilio M.R., Cross H., Fernandez-Ruiz J., French J., Hill C., Katz R., Di Marzo V., Jutras-Aswad D., Notcutt W.G., et al. Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55:791–802. doi: 10.1111/epi.12631. PubMed DOI PMC

O’Connell B.K., Gloss D., Devinsky O. Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy Behav. 2017;70:341–348. doi: 10.1016/j.yebeh.2016.11.012. PubMed DOI

Lodzki M., Godin B., Rakou L., Mechoulam R., Gallily R., Touitou E. Cannabidiol—Transdermal delivery and anti-inflammatory effect in a murine model. J. Control. Release. 2004;93:377–387. doi: 10.1016/j.jconrel.2003.09.001. PubMed DOI

Lee H., Song C., Baik S., Kim D., Hyeon T., Kim D.-H. Device-assisted transdermal drug delivery. Adv. Drug Deliv. Rev. 2018;127:35–45. doi: 10.1016/j.addr.2017.08.009. PubMed DOI

Wang W., Xue C., Mao X. Chitosan: Structural modification, biological activity and application. Int. J. Biol. Macromol. 2020;164:4532–4546. doi: 10.1016/j.ijbiomac.2020.09.042. PubMed DOI

Bernkop-Schnürch A., Dünnhaupt S. Chitosan-based drug delivery systems. Eur. J. Pharm. Biopharm. 2012;81:463–469. doi: 10.1016/j.ejpb.2012.04.007. PubMed DOI

Mohammed M.A., Syeda J.T.M., Wasan K.M., Wasan E.K. An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery. Pharmaceutics. 2017;9:53. doi: 10.3390/pharmaceutics9040053. PubMed DOI PMC

Parhi R. Drug delivery applications of chitin and chitosan: A review. Environ. Chem. Lett. 2020;18:577–594. doi: 10.1007/s10311-020-00963-5. DOI

Nair S.S. Chitosan-based transdermal drug delivery systems to overcome skin barrier functions. J. Drug Deliv. Ther. 2019;9:266–270. doi: 10.22270/jddt.v9i1.2180. DOI

Ali A., Ahmed S. A review on chitosan and its nanocomposites in drug delivery. Int. J. Biol. Macromol. 2018;109:273–286. doi: 10.1016/j.ijbiomac.2017.12.078. PubMed DOI

Potaś J., Szymańska E., Winnicka K. Challenges in developing of chitosan—Based polyelectrolyte complexes as a platform for mucosal and skin drug delivery. Eur. Polym. J. 2020;140:110020. doi: 10.1016/j.eurpolymj.2020.110020. DOI

Jeong H.J., Nam S.J., Song J.G., Park S.N. Synthesis and physicochemical properties of pH-sensitive hydrogel based on carboxymethyl chitosan/2-hydroxyethyl acrylate for transdermal delivery of nobiletin. J. Drug Deliv. Sci. Technol. 2019;51:194–203. doi: 10.1016/j.jddst.2019.02.029. DOI

Nair R.S., Morris A., Billa N., Leong C.O. An Evaluation of Curcumin-Encapsulated Chitosan Nanoparticles for Transdermal Delivery. AAPS PharmSciTech. 2019;20:69. doi: 10.1208/s12249-018-1279-6. PubMed DOI

Castilla-Casadiego D.A., Carlton H., Gonzalez-Nino D., Miranda-Muñoz K.A., Daneshpour R., Huitink D., Prinz G., Powell J., Greenlee L., Almodovar J. Design, Characterization, and Modeling of a Chitosan Microneedle Patch for Transdermal Delivery of Meloxicam as a Pain Management Strategy for Use in Cattle. Mater. Sci. Eng. C. 2021;118:111544. doi: 10.1016/j.msec.2020.111544. PubMed DOI

Dhakshinamoorthy A., Jacob M., Vignesh N.S., Varalakshmi P. Pristine and modified chitosan as solid catalysts for catalytic and biodiesel production: A minireview. Int. J. Biol. Macromol. 2020 doi: 10.1016/j.ijbiomac.2020.10.216. in press. PubMed DOI

Thein-Han W.W., Stevens W.F. Transdermal delivery controlled by a chitosan membrane. Drug Dev. Ind. Pharm. 2004;30:397–404. doi: 10.1081/DDC-120030934. PubMed DOI

Radwan-Pragłowska J., Janus Ł., Piątkowski M., Sierakowska A., Matysek D. ZnO nanorods functionalized with chitosan hydrogels crosslinked with azelaic acid for transdermal drug delivery. Colloids Surf. B. 2020;194:111170. doi: 10.1016/j.colsurfb.2020.111170. PubMed DOI

Kumaresapillai N., Basha R.A., Sathish R. Production and Evaluation of Chitosan from Aspergillus Niger MTCC Strains. Iran. J. Pharm. Sci. 2011;10:14–23. PubMed PMC

Abdel-Gawad K.M., Hifney A.F., Fawzy M.A., Gomaa M. Technology optimization of chitosan production from Aspergillus niger biomass and its functional activities. Food Hydrocoll. 2017;63:593–601. doi: 10.1016/j.foodhyd.2016.10.001. DOI

Wang Y., Li J., Hong R. Large scale synthesis of ZnO nanoparticles via homogeneous precipitation. J. Cent. South Univ. 2012;19:863–868. doi: 10.1007/s11771-012-1084-4. DOI

Ludi B. Niederberger, Zinc oxide nanoparticles: Chemical mechanisms and classical and non-classical crystallization. Dalton Trans. 2013;42:12554–12568. doi: 10.1039/c3dt50610j. PubMed DOI

Talam S., Karumuri S.R., Gunnam N. Synthesis, Characterization, and Spectroscopic Properties of ZnO Nanoparticles. ISRN Nanotechnol. 2012;2012:1–6. doi: 10.5402/2012/372505. DOI

Huang X., Zheng X., Xu Z., Yi C. ZnO-based nanocarriers for drug delivery application: From passive to smart strategies. Int. J. Pharm. 2017;534:190–194. doi: 10.1016/j.ijpharm.2017.10.008. PubMed DOI

Martínez-Carmona M., Gun’ko Y., Vallet-Regí M. ZnO Nanostructures for Drug Delivery and Theranostic Applications. Nanomaterials. 2018;8:268. doi: 10.3390/nano8040268. PubMed DOI PMC

Dorado J., Almendros G., Field J.A., Sierra-Alvarez R. Infrared spectroscopy analysis of hemp (Cannabis sativa) after selective delignification by Bjerkandera sp. at different nitrogen levels. Enzyme Microb. Technol. 2001;28:550–559. doi: 10.1016/S0141-0229(00)00363-X. PubMed DOI

Takeuchi I., Suzuki T., Makino K. Iontophoretic transdermal delivery using chitosan-coated PLGA nanoparticles for transcutaneous immunization. Colloids Surf. A Physicochem. Eng. Asp. 2021;608:125607. doi: 10.1016/j.colsurfa.2020.125607. DOI

Mikolaszek B., Kazlauske J., Larsson A., Sznitowska M. Controlled Drug Release by the Pore Structure in Polydimethylsiloxane Transdermal Patches. Polymers. 2020;12:1520. doi: 10.3390/polym12071520. PubMed DOI PMC

Wahba M.I. Enhancement of the mechanical properties of chitosan. J. Biomater. Sci. Polym. Ed. 2020;31:350–375. doi: 10.1080/09205063.2019.1692641. PubMed DOI

Ren L., Yan X., Zhou J., Tong J., Su X. Influence of chitosan concentration on mechanical and barrier properties of corn starch/chitosan films. Int. J. Biol. Macromol. 2017;105:1636–1643. doi: 10.1016/j.ijbiomac.2017.02.008. PubMed DOI

Xu R., Xia H., He W., Li Z., Zhao J., Liu B., Wang Y., Lei O., Kong Y., Bai Y., et al. Controlled water vapor transmission rate promotes wound-healing via wound re-epithelialization and contraction enhancement. Sci. Rep. 2016;6:24596. doi: 10.1038/srep24596. PubMed DOI PMC