pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»10.33380/2305-2066-2021-10-4-117-127pharmjournal-1071Research ArticleФАРМАЦЕВТИЧЕСКАЯ ТЕХНОЛОГИЯPHARMACEUTICAL TECHNOLOGYИнтраназальное введение как способ доставки лекарств в головной мозг (обзор)Intranasal Administration as a Route to Deliver Drugs to the Brain (Review)https://orcid.org/0000-0002-7110-2093ПорфирьеваН. Н.PorfiryevaN. N.

420126, Республика Татарстан, Казань, ул. Фатыха Амирхана, д. 16

Natalia N. Porfiryeva

16, Fatykha Amirkhan str., Kazan, Republic of Tatarstan, 420126

https://orcid.org/0000-0003-3515-0845СеминаИ. И.SeminaI. I.

420012, Республика Татарстан, Казань, ул. Толстого, д. 6

Irina I. Semina

6, Tolstoy str., Kazan, Republic of Tatarstan, 420012

https://orcid.org/0000-0002-0916-2853МустафинР. И.MoustafineR. I.

Мустафин Руслан Ибрагимович

420126, Республика Татарстан, г. Казань, ул. Фатыха Амирхана, д. 16; 420012, Республика Татарстан, Казань, ул. Толстого, д. 6

Rouslan I. Moustafine

16, Fatykha Amirkhan str., Kazan, Republic of Tatarstan, 420126; 6, Tolstoy str., Kazan, Republic of Tatarstan, 420012

rouslan.moustafine@gmail.comhttps://orcid.org/0000-0002-7221-2630ХуторянскийВ. В.KhutoryanskiyV. V.

420126, Республика Татарстан, г. Казань, ул. Фатыха Амирхана, д. 16; Whiteknights, PO box 224, Reading RG66AD

Vitaliy V. Khutoryanskiy

16, Fatykha Amirkhan str., Kazan, Republic of Tatarstan, 420126; Whiteknights, PO box 224, Reading RG66AD

Институт фармации, ФГБОУ ВО Казанский ГМУ Минздрава РоссииInstitute of Pharmacy, Kazan State Medical UniversityЦентральная научно-исследовательская лаборатория, ФГБОУ ВО Казанский ГМУ Минздрава РоссииCentral Research Laboratory, Kazan State Medical UniversityИнститут фармации, ФГБОУ ВО Казанский ГМУ Минздрава России; Центральная научно-исследовательская лаборатория, ФГБОУ ВО Казанский ГМУ Минздрава РоссииInstitute of Pharmacy, Kazan State Medical University; Central Research Laboratory, Kazan State Medical UniversityИнститут фармации, ФГБОУ ВО Казанский ГМУ Минздрава России; Reading School of Pharmacy, University of ReadingInstitute of Pharmacy, Kazan State Medical University; Reading School of Pharmacy, University of Reading202124112021104117127Copyright © Порфирьева Н.Н., Семина И.И., Мустафин Р.И., Хуторянский В.В., 20212021Порфирьева Н.Н., Семина И.И., Мустафин Р.И., Хуторянский В.В.Porfiryeva N.N., Semina I.I., Moustafine R.I., Khutoryanskiy V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/1071Введение

Введение. Интраназальная доставка лекарственных средств напрямую из носа в мозг является одним из многообещающих направлений для лечения заболеваний головного мозга, включающих нейродегенеративные расстройства, инсульт, опухоли головного мозга и т. д.

Текст

Текст. Доставка лекарства через нос имеет ряд преимуществ, среди которых быстрое наступление фармакологического эффекта, возможность обхода гематоэнцефалического барьера, снижение вероятности возникновения побочных эффектов, а также быстрый и неинвазивный способ введения. Однако существенными недостатками данного пути является сравнительно быстрое вымывание с поверхности слизистой оболочки, плохое проникновение лекарства через слизистую носа, мукоцилиарный клиренс и действие протеолитических ферментов. В настоящее время для преодоления вышеуказанных ограничений используются различные направления, среди которых следует отметить разработку систем доставки из носа в мозг, представляющих собой мукоадгезивные, мукус-проникающие и гелеобразующие системы, способствующие удерживанию или проникновению лекарств через слизистую оболочку. При этом значительную роль при конструировании такого рода систем занимают высокомолекулярные соединения. В частности, мукоадгезивные системы могут быть получены из катионных и анионных полимеров. Недавние исследования также показали проявление мукоадгезивных свойств у интерполиэлектролитных комплексов. Увеличение мукоадгезивных свойств полимеров при конструировании систем доставки лекарств может быть также достигнуто путем присоединения к ним различных функциональных групп, таких как тиолы, малеимиды, акрилаты, метакрилаты, катехолы и т. д. Мукус-проникающие системы могут быть получены путем ПЭГилирования наночастиц, а также функционализацией с помощью некоторых поли-(2-оксазолинов), поливинилового спирта и др., что было показано на других слизистых оболочках организма. Наконец, увеличение проникновения возможно достичь путем использования муколитических средств в комбинации с неионогенными поверхностно-активными веществами. Другим подходом для увеличения эффективности доставки лекарств из носа в мозг является использование гелеобразующих систем. В частности, актуальным является гелеобразование in situ. Данный вид гелей на первом этапе представляет собой раствор, в дальнейшем в ответ на химическое и физическое воздействие происходит фазовый переход, сопровождающийся образованием геля. В зависимости от внешней стимуляции фазового перехода различают термо-, рН-, ионообратимые и другие системы, показавшие свою эффективность для доставки в мозг путем интраназального введения.

Заключение

Заключение. Эффективная интраназальная доставка лекарственных средств и терапевтических агентов в мозг может быть достигнута путем использования мукоадгезивных, мукус-проникающих и гелеобразующих систем и/или их комбинаций.

Introduction

Introduction. Intranasal drug delivery from nose-to-brain is one of the promising approaches for the treatment of brain diseases including neurodegenerative diseases, stroke, brain tumors, etc.

Text

Text. Delivery of drugs through the nose has a number of advantages, including the rapid onset of a pharmacological effect, the ability to bypass the blood-brain barrier, avoidance of some side effects and fast and non-invasive route of administration. However, the significant disadvantages of this route are rapid elimination of the drug from the surface of the mucosal membrane, poor penetration of the drug through the nasal mucosa, mucociliary clearance and effects of proteolytic enzymes. Currently, to overcome the above limitations, various approaches are used, including the development of delivery systems from nose-to-brain, which are mucoadhesive, mucus-penetrating and gel-forming systems that facilitate the retention or penetration of drugs through the mucosal membranes. At the same time, high-molecular weight compounds play a significant role in the design of these systems. In particular, mucoadhesive systems can be prepared from cationic and anionic polymers. Recent studies have also shown that interpolyelectrolyte complexes also exhibit mucoadhesive properties. An improvement in mucoadhesive properties of polymers can also be achieved by conjugating various functional groups such as thiols, maleimides, acrylates, methacrylates, catechols, etc. Mucus-penetrating systems can be prepared by PEGylation of nanoparticles, as well as functionalization with some poly(2-oxazolines), polyvinyl alcohol, etc. The mucus-penetrating ability of these polymers has been shown in other mucosal membranes in the body. Finally, increased penetration can be achieved by using mucolytic agents in combination with non-ionic surfactants. Another approach to increase the efficiency of drug delivery from nose-to-brain is the use of in situ gelling systems. Initially, this type of formulation exists as a solution; then a phase transition to gel is observed in response to chemical and physical effects. Depending on the external stimulation of the phase transition, thermo-, pH-, ion-reversible and other systems are known. These systems have shown effectiveness for delivery to the brain by intranasal administration.

Conclusion

Conclusion. Effective intranasal delivery of drugs and therapeutic agents to the brain can be achieved by using mucoadhesive, mucus-penetrating, gelling systems and/or their combinations.

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The authors declare that there are no conflicts of interest present.