Molecular mechanisms of transport of substances across the blood-brain barrie as targets for pharmacological action. Part 2. Modern methods of delivery of pharmacological agents to the central nervous system
- Authors: Litvinova M.V.1,2, Trofimov A.N.1,2, Shabanov P.D.2, Lebedev A.A.2, Bychkov E.R.2, Arseniev N.А.1, Tyukavin A.I.1
-
Affiliations:
- Saint Petersburg Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation
- Institute of Experimental Medicine
- Issue: Vol 4, No 3 (2022)
- Pages: 82-96
- Section: Actual problems: discussion tribune
- URL: https://journals.rcsi.science/PharmForm/article/view/132715
- DOI: https://doi.org/10.17816/phf120109
- ID: 132715
Cite item
Full Text
Abstract
One of the unresolved problems on the way to improving the pharmacotherapy of CNS diseases is the development and creation of technologies that allow drugs to cross the blood-brain barrier (BBB). The review discusses modern methods of drug delivery to the CNS. The advantages and disadvantages of the main pharmacological strategies for directly overcoming the BBB and an alternative to this are shown. New methods of drug delivery to the brain with damage (physical, chemical, etc.) and without disruption of the blood-brain barrier structure (small molecules, cell-mediated transport, stem cells) are considered. The prospects for the use of artificial nanosized drug transporters are discussed. An alternative strategy of pharmacological action on the CNS structures (intranasal route) is shown to be promising. Possible mechanisms of action of pharmacological agents on CNS structures bypassing the BBB are considered.
Full Text
##article.viewOnOriginalSite##About the authors
Maria V. Litvinova
Saint Petersburg Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation; Institute of Experimental Medicine
Author for correspondence.
Email: litvinova-masha@bk.ru
Ph.D. Student at the S.V. Anichkov Department of Neuropharmacology, Laboratory Assistant at the Department of Physiology and Pathology
Russian Federation, Saint Petersburg; Saint PetersburgAlexander N. Trofimov
Saint Petersburg Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation; Institute of Experimental Medicine
Email: alexander.n.trofimov@gmail.com
Ph.D. of Biological Sciences, Senior Researcher at the I.P. Pavlov Department of Physiology, Associate Professor at the Department of Physiology and Pathology
Russian Federation, Saint Petersburg; Saint PetersburgPetr D. Shabanov
Institute of Experimental Medicine
Email: pdshabanov@mail.ru
Dr. of Med. Sci. (Pharmacology), Professor and Head, S. V. Anichkov Dept. of Neuropharmacology
Russian Federation, Saint PetersburgAndrei A. Lebedev
Institute of Experimental Medicine
Email: aalebedev-iem@rambler.ru
ORCID iD: 0000-0003-0297-0425
SPIN-code: 4998-5204
Dr. Biol. Sci. (Pharmacol-ogy), Professor, Leading Researcher, S. V. Anichkov Dept. of Neuropharmacology
Russian Federation, Saint PetersburgEvgeny R. Bychkov
Institute of Experimental Medicine
Email: bychkov@mail.ru
ORCID iD: 0000-0002-8911-6805
SPIN-code: 9408-0799
PhD (Biochemistry), Senior Re-searcher, S. V. Anichkov Dept. of Neuropharmacology
Russian Federation, Saint PetersburgNikolay А. Arseniev
Saint Petersburg Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation
Email: nikolay.arseniev@pharminnotech.com
SPIN-code: 9038-7623
Ph.D, Biology, docent, docent of the Department to Physiology and Pathology
Russian Federation, Saint PetersburgAlexander I. Tyukavin
Saint Petersburg Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation
Email: alexander.tukavin@pharminnotech.com
SPIN-code: 8476-5366
Dr. of Medicine (MD), Professor, Head of the Department to Physiology and Pathology
Russian Federation, Saint PetersburgReferences
- Terstappen G. C., Meyer A. H., Bell R. D., Zhang W. Strategies for delivering therapeutics across the blood-brain barrier. Nat Rev Drug Discov. 2021 May;20 (5):362-383. doi: 10.1038/s41573-021-00139-y. Epub 2021 Mar 1. PMID: 33649582.
- Gandhi K., Barzegar-Fallah A., Banstola A., Rizwan S. B., Reynolds J. N. J. Ultrasound-Mediated Blood-Brain Barrier Disruption for Drug Delivery: A Systematic Review of Protocols, Efficacy, and Safety Outcomes from Preclinical and Clinical Studies. Pharmaceutics. 2022 Apr 11;14(4):833. doi: 10.3390/pharmaceutics14040833. PMID: 35456667; PMCID: PMC9029131.
- Frim D. M., Uhler T. A., Galpern W. R., Beal M. F., Breakefield X. O., Isacson O. Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. Proc. Natl. Acad. Sci. USA. 1994;91:5104–5108. doi: 10.1073/pnas.91.11.5104.
- Pardridge W. M. The Blood-Brain Barrier: Bottleneck in Brain Drug Development. NeuroRx. 2005;2:3–14. doi: 10.1602/neurorx.2.1.3. [PMC free article] [PubMed] [CrossRef] [Google Scholar] [Ref list]
- Aryal M., Arvanitis C. D., Alexander P. M., McDannold N. Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system. Adv. Drug Deliv. Rev. 2014;72:94–109. doi: 10.1016/j.addr.2014.01.008.
- Abrahao A., Meng Y., Llinas M., Huang Y., Hamani C., Mainprize T., Aubert I., Heyn C., Black S. E., Hynynen K., et al. First-in-human trial of blood-brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound. Nat. Commun. 2019;10:4373. doi: 10.1038/s41467-019-12426-9.
- Goldwirt L., Canney M., Horodyckid C., Poupon J., Mourah S., Vignot A., Chapelon J. Y., Carpentier A. Enhanced brain distribution of carboplatin in a primate model after blood-brain barrier disruption using an implantable ultrasound device. Cancer Chemother. Pharmacol. 2016;77: 211–216. doi: 10.1007/s00280-015-2930-5.
- Lipsman N., Meng Y., Bethune A. J., Huang Y., Lam B., Masellis M., Herrmann N., Heyn C., Aubert I., Boutet A., et al. Blood-brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound. Nat. Commun. 2018;9:2336. doi: 10.1038/s41467-018-04529-6.
- Mainprize T., Lipsman N., Huang Y., Meng Y., Bethune A., Ironside S., Heyn C., Alkins R., Trudeau M., Sahgal A., et al. Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study. Sci. Rep. 2019;9:321. doi: 10.1038/s41598-018-36340-0.
- Dauba A., Delalande A., Kamimura H. A. S., Conti A., Larrat B., Tsapis N., Novell A. Recent Advances on Ultrasound Contrast Agents for Blood-Brain Barrier Opening with Focused Ultrasound. Pharmaceutics. 2020 Nov 21;12(11):1125. doi: 10.3390/pharmaceutics12111125. PMID: 33233374; PMCID: PMC7700476.
- Kovacs Z. I., Kim S., Jikaria N., Qureshi F., Milo B., Lewis B. K., Bresler M., Burks S. R., Frank J. A. Disrupting the blood-brain barrier by focused ultrasound induces sterile inflammation. Proc. Natl. Acad. Sci. USA. 2017;114:E75–E84. doi: 10.1073/pnas.1614777114.
- Tsai H. C., Tsai C. H., Chen W. S., Inserra C., Wei K. C., Liu H. L. Safety evaluation of frequent application of microbubble-enhanced focused ultrasound blood-brain-barrier opening. Sci. Rep. 2018; 8:17720. doi: 10.1038/s41598-018-35677-w.
- Morad G., Carman C. V., Hagedorn E. J., Perlin J. R., Zon L. I.., Mustafaoglu N., Park T. E., Ingber D. E., Daisy C. C., Moses M. A. Tumor-Derived Extracellular Vesicles Breach the Intact Blood-Brain Barrier via Transcytosis. ACS Nano. 2019 Dec 24;13(12):13853-13865. doi: 10.1021/acsnano.9b04397. Epub 2019 Sep 10. PMID: 31479239; PMCID: PMC7169949.
- Pathology / A. I. Tyukavin, A. G. Vasiliev, T. D. Vlasov [and others]. - Moscow: Limited Liability Company “Scientific Publishing Center INFRA-M”, 2020. – 844 p. – (Higher education: Specialist). – ISBN 978-5-16-016260-7. – doi: 10.12737/1090595.
- Whelan R., Hargaden G. C., Knox A. J. S. Modulating the Blood-Brain Barrier: A Comprehensive Review. Pharmaceutics. 2021 Nov 22;13(11):1980. doi: 10.3390/pharmaceutics13111980. PMID: 34834395; PMCID: PMC8618722.
- Haney M. J., Zhao Y., Harrison E. B., Mahajan V., Ahmed S., He Z., Suresh P., Hingtgen S. D., Klyachko N. L., Mosley R. L., Gendelman H. E., Kabanov A. V., Batrakova E. V. Specific transfection of inflamed brain by macrophages: a new therapeutic strategy for neurodegenerative diseases. PLoS One. 2013 Apr 19;8(4):e61852. doi: 10.1371/journal.pone.0061852. PMID: 23620794; PMCID: PMC3631190.
- Patil S. M., Sawant S. S., Kunda N. K. Exosomes as drug delivery systems: A brief overview and progress update. Eur J Pharm Biopharm. 2020 Sep;154: 259-269. doi: 10.1016/j.ejpb.2020.07.026. Epub 2020 Jul 25. PMID: 32717385.
- Lo Furno D., Mannino G., Giuffrida R. Functional role of mesenchymal stem cells in the treatment of chronic neurodegenerative diseases. Journal of Cellular Physiology. 2018;233(5):3982–3999. doi: 10.1002/jcp.26192.; Salem N. A. Mesenchymal stem cell based therapy for Parkinson’s disease. International Journal of Stem Cell Research & Therapy. 2019;6(1):p. 62. doi: 10.23937/2469-570x/1410062
- Chia Y. C., Anjum C. E., Yee H. R., Kenisi Y., Chan M. K. S., Wong M. B. F., Pan S. Y. Stem Cell Therapy for Neurodegenerative Diseases: How Do Stem Cells Bypass the Blood-Brain Barrier and Home to the Brain? Stem Cells Int. 2020 Sep 4;2020:8889061. doi: 10.1155/2020/8889061. PMID: 32952573; PMCID: PMC7487096
- Soper B. W., Duffy T. M., Lessard M. D., Jude C. D., Schuldt A. J., Vogler C. A., Levy B., Barker J. E. Transplanted ER-MP12hi20-58med/hi myeloid progenitors produce resident macrophages from marrow that are therapeutic for lysosomal storage disease. Blood Cells Mol Dis. 2004 Jan-Feb;32(1):199-213. doi: 10.1016/j.bcmd.2003.09.003. PMID: 14757436.
- Bulbake U., Doppalapudi S., Kommineni N., Khan W. Liposomal Formulations in Clinical Use: An Updated Review. Pharmaceutics. 2017;9:12. doi: 10.3390/pharmaceutics9020012.
- Yetisgin A. A., Cetinel S., Zuvin M., Kosar A., Kutlu O. Therapeutic Nanoparticles and Their Targeted Delivery Applications. Molecules. 2020;25:2193. doi: 10.3390/molecules25092193.
- Teleanu R. I., Preda M. D., Niculescu A. G., Vladâcenco O., Radu C. I., Grumezescu A. M., Teleanu D. M. Current Strategies to Enhance Delivery of Drugs across the Blood-Brain Barrier. Pharmaceutics. 2022 May 4;14(5):987. doi: 10.3390/pharmaceutics14050987. PMID: 35631573; PMCID: PMC9145636.
- Loyse A., Thangaraj H., Easterbrook P., Ford N., Roy M., Chiller T., Govender N., Harrison T. S., Bicanic T. Cryptococcal meningitis: Improving access to essential antifungal medicines in resource-poor countries. Lancet Infect. Dis. 2013;13:629–637. doi: 10.1016/S1473-3099(13)70078-1.
- Yetisgin A. A., Cetinel S., Zuvin M., Kosar A., Kutlu O. Therapeutic Nanoparticles and Their Targeted Delivery Applications. Molecules. 2020; 25:2193. doi: 10.3390/molecules25092193.
- Hersh A. M., Alomari S., Tyler B. M. Crossing the Blood-Brain Barrier: Advances in Nanoparticle Technology for Drug Delivery in Neuro-Oncology. Int J Mol Sci. 2022 Apr 9;23(8):4153. doi: 10.3390/ijms23084153. PMID: 35456971; PMCID: PMC9032478
- Mitchell M. J., Billingsley M. M., Haley R. M., Wechsler M. E., Peppas N. A., Langer R. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 2021;20:101–124. doi: 10.1038/s41573-020-0090-8.
- Thorne R. G., Pronk G. J., Padmanabhan V., Frey W. H. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience. 2004;127: 481–496. doi: 10.1016/j.neuroscience.2004.05.029.
- Mitusova K., Peltek O. O., Karpov T. E., Muslimov A. R., Zyuzin M. V., Timin A. S.. Overcoming the blood-brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches. J Nanobiotechnology. 2022 Sep 15;20(1):412. doi: 10.1186/s12951-022-01610-7. PMID: 36109754; PMCID: PMC9479308.
- Lochhead J. J., Wolak D. J., Pizzo M. E., Thorne R. G. Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration. J Cereb Blood Flow Metab. 2015 Mar;35(3):371-81. doi: 10.1038/jcbfm.2014.215. Epub 2014 Dec 10. PMID: 25492117; PMCID: PMC4348383.
- Lochhead J. J., Thorne R. G. Intranasal delivery of biologics to the central nervous system. Adv Drug Deliv Rev. 2012 May 15;64(7):614-28. doi: 10.1016/j.addr.2011.11.002. Epub 2011 Nov 15. PMID: 22119441.
- Knox E. G., Aburto M. R., Clarke G., Cryan J. F., O’Driscoll C. M. The blood-brain barrier in aging and neurodegeneration. Mol Psychiatry. 2022 Jun;27(6): 2659-2673. doi: 10.1038/s41380-022-01511-z. Epub 2022 Mar 31. PMID: 35361905; PMCID: PMC9156404.
- National Center for Biotechnology Information PubChem Patent Summary for WO9107947-A1. [(accessed on 16 April 2022)]; Available online: https://pubchem.ncbi.nlm.nih.gov/patent/WO-9107947-A1. Дата обращения: ноябрь 2022 30.
- Costa C. P., Moreira J. N., Sousa Lobo J. M., & Silva A. C. (2021). Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: A current overview of in vivo studies. Acta pharmaceutica Sinica. B, 11(4), 925–940. https://doi.org/10.1016/j.apsb.2021.02.012
- Rompicherla S. K. L., Arumugam K., Bojja S. L., Kumar N., Rao C. M. Pharmacokinetic and pharmacodynamic evaluation of nasal liposome and nanoparticle based rivastigmine formulations in acute and chronic models of Alzheimer’s disease. NaunynSchmiedeberg’s Arch. Pharmacol. 2021;394:1737–1755. doi: 10.1007/s00210-021- 02096-0.