Введение

pharmjournal

Разработка и регистрация лекарственных средств

Drug development & registration

2305-20662658-5049

LLC «CPHA»

10.33380/2305-2066-2021-10-4-54-63

pharmjournal-1066

Research Article

ФАРМАЦЕВТИЧЕСКАЯ ТЕХНОЛОГИЯ

PHARMACEUTICAL TECHNOLOGY

Интраназальные системы доставки in situ: перспективы применения и основные фармацевтические аспекты разработки (обзор)

In situ Intranasal Delivery Systems: Application Prospects and Main Pharmaceutical Aspects of Development (Review)

https://orcid.org/0000-0001-8695-0346

Бахрушина

Е. О.

Bakhrushina

E. O.

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Elena O. Bakhrushina

8/2, Trubetskaya str., Moscow, 119991

https://orcid.org/0000-0003-4307-8791

Демина

Н. Б.

Demina

N. B.

Демина Наталья Борисовна

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Natalia B. Demina

8/2, Trubetskaya str., Moscow, 119991

nbd217@mail.ru

https://orcid.org/0000-0002-4448-2588

Шумкова

М. М.

Shumkova

M. M.

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Marina M. Shumkova

8/2, Trubetskaya str., Moscow, 119991

https://orcid.org/0000-0001-8678-8051

Родюк

П. С.

Rodyuk

P. S.

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Polina S. Rodyuk

8/2, Trubetskaya str., Moscow, 119991

https://orcid.org/0000-0002-8418-6177

Шуликина

Д. С.

Shulikina

D. S.

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Daria S. Shulikina

8/2, Trubetskaya str., Moscow, 119991

https://orcid.org/0000-0002-7242-2988

Краснюк

И. И.

Krasnyuk

I. I.

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Ivan I. Krasnyuk

8/2, Trubetskaya str., Moscow, 119991

ФГАОУ ВО Первый МГМУ им. И. М. Сеченова Минздрава России (Сеченовский университет)I.M. Sechenov First MSMU of the Ministry of Health of the Russian Federation (Sechenov University)

2021

23112021

1045463

2021

Бахрушина Е.О., Демина Н.Б., Шумкова М.М., Родюк П.С., Шуликина Д.С., Краснюк И.И.

Bakhrushina E.O., Demina N.B., Shumkova M.M., Rodyuk P.S., Shulikina D.S., Krasnyuk I.I.

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/1066

Введение

Введение. Интраназальная доставка in situ гелеобразующих систем является сложным, но перспективным направлением. Из-за высокой стоимости разработки нового химического объекта или генно-инженерной модификации биологических молекул фармацевтические компании сосредоточиваются на разработке технологий новых систем доставки для существующих активных фармацевтических ингредиентов с целью улучшения их эффективности и биодоступности. In situ системы для интраназальной доставки за счет повышенной вязкости и мукоадгезии к слизистой носа позволяют преодолевать мукоцилиарный клиренс и гарантировать полное всасывание и пролонгированное высвобождение активных фармацевтических ингредиентов.

Текст

Текст. В статье рассмотрены виды и основные преимущества интраназальных in situ систем доставки, показанные в доклинических исследованиях, а также подходы к технологии получения и стандартизации этих систем. Обобщены данные научных исследований в этой области за последние 15 лет, выделены наиболее перспективные полимеры для создания термообратимых и рН-чувствительных композиций, а также проанализированы современные методы оценки золь-гель перехода in situ.

Заключение

Заключение. Применение in situ систем для интраназального введения позволяет обеспечивать высокую таргетность доставки синтетических и биологических молекул в мозг. В настоящее время имеются многочисленные фармакокинетические и фармакодинамические исследования на животных, подтверждающие эффективность таких систем, а также их безопасность. Наиболее востребованными для конструирования систем доставки in situ остаются термореверсивные коммерчески доступные и направленно синтезируемые полимеры (полоксамер 407, PLGA, NIPAAm и др.), а также хитозан. Для оценки параметров in situ гелеобразования широко используются in vitro и ex vivo методы со слизистой и искусственной назальной жидкостью, однако для увеличения воспроизводимости методик и улучшения корреляции in vitro/in vivo рекомендуется проводить моделирование носовой полости. Совершенствование технологии и методов скриннинга интраназальных реверсивных систем поможет приблизиться к проведению клинических исследований и выходу этих систем доставки на мировой фармацевтический рынок.

Introduction

Introduction. Intranasal delivery of in situ gel-forming systems is a complex but promising direction. Due to the high cost of developing a new chemical object or genetically engineered modification of biological molecules, pharmaceutical companies are focusing on developing technologies for new delivery systems for existing active pharmaceutical ingredients to improve their effectiveness and bioavailability. In situ systems for intranasal delivery, due to increased viscosity and mucoadhesion to the nasal mucosa, allow overcoming mucociliary clearance and ensuring complete absorption and prolonged release of drugs.

Text

Text. The article discusses the main advantages of intranasal in situ delivery systems shown in preclinical studies, as well as approaches to the technology of obtaining and standardization of these systems. The results of scientific research in this field over the past 15 years are summarized, the most promising polymers for creating thermoreversible and pH-sensitive compositions are identified, and modern methods for evaluating the sol-gel transition in situ are analyzed.

Conclusion

Conclusion. The use of in situ systems for intranasal administration allows providing a high targeting of the delivery of synthetic and biological molecules to the brain. Currently, numerous pharmacokinetic and pharmacodynamic preclinical studies confirm the effectiveness of such systems, as well as their safety. Thermoreversible commercially available and directionally synthesized polymers (poloxamer 407, PLGA, NIPAAm, etc.), as well as chitosan, remain the most popular for the design of in situ delivery systems. In vitro and ex vivo methods with mucosa and artificial nasal fluid are widely used to assess the parameters of in situ gelation, but to increase the reproducibility of the methods and improve the correlation in vitro/in vivo, it is recommended to conduct modeling of the nasal cavity. Developing the technology and methods of screening of intranasal reversible systems will help to get closer to clinical trials and the entry of these delivery systems into the global pharmaceutical market.

интраназальная доставкасистемы доставкиin situ гелеобразованиеполоксамерыхитозанмукоадгезия

intranasal deliverydelivery systemsin situ gelationpoloxamerschitosanmucoadhesion

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