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

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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.

作者简介

Maria Litvinova

Saint Petersburg Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation; Institute of Experimental Medicine

编辑信件的主要联系方式.
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

俄罗斯联邦, Saint Petersburg; Saint Petersburg

Alexander 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

俄罗斯联邦, Saint Petersburg; Saint Petersburg

Petr Shabanov

Institute of Experimental Medicine

Email: pdshabanov@mail.ru

Dr. of Med. Sci. (Pharmacology), Professor and Head, S. V. Anichkov Dept. of Neuropharmacology

俄罗斯联邦, Saint Petersburg

Andrei Lebedev

Institute of Experimental Medicine

Email: aalebedev-iem@rambler.ru
ORCID iD: 0000-0003-0297-0425
SPIN 代码: 4998-5204

Dr. Biol. Sci. (Pharmacol-ogy), Professor, Leading Researcher, S. V. Anichkov Dept. of Neuropharmacology

俄罗斯联邦, Saint Petersburg

Evgeny Bychkov

Institute of Experimental Medicine

Email: bychkov@mail.ru
ORCID iD: 0000-0002-8911-6805
SPIN 代码: 9408-0799

PhD (Biochemistry), Senior Re-searcher, S. V. Anichkov Dept. of Neuropharmacology

俄罗斯联邦, Saint Petersburg

Nikolay Arseniev

Saint Petersburg Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation

Email: nikolay.arseniev@pharminnotech.com
SPIN 代码: 9038-7623

Ph.D, Biology, docent, docent of the Department to Physiology and Pathology

俄罗斯联邦, Saint Petersburg

Alexander Tyukavin

Saint Petersburg Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation

Email: alexander.tukavin@pharminnotech.com
SPIN 代码: 8476-5366

Dr. of Medicine (MD), Professor, Head of the Department to Physiology and Pathology

俄罗斯联邦, Saint Petersburg

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2. Fig. 1. Methods of drug delivery through the blood-brain barrier

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3. Fig. 2. Mechanism of modulation of the blood-brain barrier by focused ultrasound. Schematic representation of several mechanisms of BBB destruction: stable cavitation causes the mechanism of pushing (a) and pulling (b) microflows (c), which can safely cross the blood-brain barrier. Inertial cavitation causes microjet (d) fragmentation (e) and shock wave (e), which can increase the risk of damage to the BBB [10]

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4. Fig. 3. Intercellular interactions through extravesicles [14]

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5. Fig. 4. Stem cells during fetal development

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6. Fig. 5. Promising transport mechanisms of liposomes to overcome the BBB

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7. Fig. 6. Extracellular mechanism of drug delivery during intranasal administration

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8. Fig. 7. Intracellular mechanism of substance delivery during intranasal administration

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