vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ17.305vavilov-1235Research ArticleТЕСТ-СИСТЕМЫ И БИОИСПЫТАНИЯTEST SYSTEMS AND BIOTESTSЭффективность ольфакторного транспорта аморфных и кристаллических наночастиц оксидов марганцаOlfactory transport efficiency of the amorphous and crystalline manganese oxide nanoparticlesРомащенкоА. В.RomashchenkoA. V.

Новосибирск.

Novosibirsk.

arom@bionet.nsc.ruПетровскийД. В.PetrovskiiD. V.

Новосибирск.

Novosibirsk.

ШараповаМ. Б. SharapovaM. B.

Новосибирск.

Novosibirsk.

МошкинЮ. М.MoshkinY. M.

Новосибирск.

Novosibirsk.

КуперК. Э.KuperK. E.

Новосибирск.

Novosibirsk.

МорозоваК. Н. MorozovaK. N.

Новосибирск.

Novosibirsk.

КиселеваЕ. В.KiselevaE. V.

Новосибирск.

Novosibirsk.

МошкинМ. П.MoshkinM. P.

Новосибирск.

Novosibirsk.

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Институт вычислительных технологий Сибирского отделения Российской академии наук.РоссияInstitute of Cytology and Genetics SB RAS; The Institute of Computational Technologies SB RAS.Russian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук.РоссияInstitute of Cytology and Genetics SB RAS.Russian FederationИнститут ядерной физики им. Г.И. Будкеpа Сибирского отделения Российской академии наук.РоссияBudker Institute of Nuclear Physics SB RAS.Russian Federation201723122017217848855Copyright © Ромащенко А.В., Петровский Д.В., Шарапова М.Б., Мошкин Ю.М., Купер К.Э., Морозова К.Н., Киселева Е.В., Мошкин М.П., 20172017Ромащенко А.В., Петровский Д.В., Шарапова М.Б., Мошкин Ю.М., Купер К.Э., Морозова К.Н., Киселева Е.В., Мошкин М.П.Romashchenko A.V., Petrovskii D.V.,  Sharapova M.B., Moshkin Y.M., Kuper K.E.,  Morozova K.N., Kiseleva E.V., Moshkin M.P.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1235

Известно, что наноразмерные твердые аэрозоли способны поступать из носовой полости в мозг в обход гематоэнцефалического барьера. Необходимость исследования факторов, влияющих на назальный транспорт наночастиц, обусловлена тем, что таким образом в мозг могут проникать как ксенобиотики, так и терапевтические препараты. Показано, что биодоступность твердых частиц определяет их размер и поверхностный заряд. Вместе с тем влияние структуры кристаллической решетки практически не исследовано. В данной работе, выполненной на половозрелых самцах мышей C57BL/6J, проанализирована эффективность поступления в ольфакторный эпителий (ОЭ) и обонятельные луковицы (ОЛ) интраназально апплицированных наночастиц оксидов марганца с аморфной и кристаллической структурой. Для оценки накопления магнито-контрастных наночастиц марганца в ОЛ и ОЭ использовали Т1-взвешенную магнитно-резонансную томографию. Установлено, что аморфные частицы накапливаются в ОЭ и ОЛ в большей степени, чем кристаллические. Одной из причин различного поступления в головной мозг интраназально введенных нанообъектов может быть неодинаковая способность аморфных и кристалических частиц преодолевать мукозальный слой, покрывающий ОЭ. Действительно, введение муколитика (дитиотреитол) за 20 мин до аппликации не увеличивало накопление в ОЭ и ОЛ аморфных частиц, но повышало эффективность поступления кристаллических наночастиц. Сведения о различном поступлении аморфных и кристаллических наночастиц из носовой полости в мозг, а также обоснование ключевой роли мукозального слоя в дифференцировании проникающей способности этих частиц будут полезны и при разработке подходов к оценке токсикологической опасности воздушной среды, и для оптимизации методов ингаляционной терапии.

The ability to deliver particulated xenobiotics and therapeutic drugs directly from the nasal cavity to the central nervous system, bypassing the hemato-encephalic barrier, determines a high importance of investigation of factors influencing this process. It was shown that the bioavailability of solid particles is influenced by their size and surface charge. At the same time, the impact of a crystal structure (crystalline/amorphous) has been poorly investigated. In this study, using sexually mature male C57BL/6J mice, we analyzed the efficiency of the nose-to-brain transport of crystalline and amorphous manganese oxide nanoparticles. T1-weighted magnetic resonance imaging (MRI) was used to evaluate the accumulation of manganese nanoparticles in olfactory bulb (OB) and olfactory epithelium (OE). So, it has been established that amorphous particles have higher accumulation rate in OE and OB in comparison with crystalline particles after their intranasal administration. The unequal ability of amorphous and crystalline particles to overcome the mucosal layer covering the OE may be one of the possible reasons for the different nose-to-brain transport efficiency of particulated matter. Indeed, the introduction of mucolytic (dithiothreitol) 20 minutes prior to intranasal particle application did not influence the accumulation of amorphous particles in OE and OB, but enhanced the efficiency of crystalline nanoparticle entry. Data on the different intake of amorphous and crystalline nanoparticles from the nasal cavity to the brain, as well as the evidence for the key role of the mucosal layer in differentiating the penetrating power of these particles will be useful in developing approaches to assessing air pollution and optimizing the methods of inhalation therapy.

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