Effect of cucurbiturils on the numbers and differential counts of peripheral blood leukocytes in laboratory animals after in vivo parenteral administration

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Immunological safety of nanoparticles is an urgent problem for development of drug delivery systems used as the basis for creating these systems. Cucurbit[n]urils (CB[n]) are molecular nanocontainers that can encapsulate various drugs and serve as the basis for delivery systems. Cucurbiturils are low-toxic compounds: under in vitro conditions, they exhibit weak immunomodulatory properties, without sufficient immunotoxicity. The aim of the present study was to evaluate the in vivo effects of cucurbiturils on the number and differential leukocyte counts in peripheral blood.

BALB/c mice aged 2-4 months were used in the work. For this study, cucurbiturils were diluted in phosphate-buffered saline and administered to laboratory animals intraperitoneally (three times a week).

When evaluating the effect of cucurbit[7]uril on blood parameters of the animals after three intraperitoneal injections weekly, no statistically significant changes were registered. However, at first administration, the animals showed a slight increase in relative number of lymphocytes after the first injection of CB[6], and an increased proportion of neutrophils after the first administration of CB[8]. Meanwhile, the proportions of lymphocytes and neutrophils were within normal ranges after the 2nd and 3rd injections of cucurbiturils, and did not show any significant differences against the controls. Moreover, the impact upon the subpopulation composition of peripheral blood lymphocytes in laboratory animals was assessed. After injection of CB[6], there was a decrease in T lymphocytes in the peripheral blood, along with increased proportion of CD19+B lymphocytes compared with the controls. CB[7] and CB[8] injections did not affect the subpopulation profile of peripheral blood lymphocytes.

We have found that intraperitoneal administration of CB[n] did not affect the blood parameters of laboratory animals, thus, probably suggesting the in vivo safety of these compounds. At the same time, CB[6] is able to exert a stimulating effect on humoral immunity by increasing relative contents of B lymphocytes.

作者简介

Ekaterina Pashkina

Research Institute of Fundamental and Clinical Immunology

编辑信件的主要联系方式.
Email: pashkina.e.a@yandex.ru
ORCID iD: 0000-0002-4912-5512

PhD (Biology), Senior Research Associate, Laboratory of Clinical Immunopathology

俄罗斯联邦, Novosibirsk

Alina Aktanova

Research Institute of Fundamental and Clinical Immunology

Email: aktanova_al@mail.ru

Junior Research Associate, Laboratory of Clinical Immunopathology

俄罗斯联邦, Novosibirsk

Ekaterina Kovalenko

A. Nikolaev Institute of Inorganic Chemistry, Siberian Branch, Russian Academy of Sciences

Email: e.a.kovalenko@niic.nsc.ru

PhD (Chemistry), Research Associate, Laboratory of Chemistry of Cluster and Supramolecular Compounds

俄罗斯联邦, Novosibirsk

Vladimir Kozlov

Research Institute of Fundamental and Clinical Immunology

Email: vakoz40@yandex.ru

PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Scientific Supervisor

俄罗斯联邦, Novosibirsk

参考

  1. Aktanova A., Abramova T., Pashkina E., Boeva O., Grishina L., Kovalenko E., Kozlov V. Assessment of the biocompatibility of cucurbiturils in blood cells. Nanomaterials (Basel), 2021, Vol. 11, no. 6, 1356. doi: 10.3390/nano11061356.
  2. Aktanova A.A., Boeva O.S., Barkovskaya M.S., Kovalenko E.A., Pashkina E.A. Influence of cucurbiturils on the production of reactive oxygen species by T and B lymphocytes, platelets and red blood cells. Int. J. Mol. Sci., 2023, Vol. 24, no. 2, 1441. doi: 10.3390/ijms24021441.
  3. Barooah N., Mohanty J., Bhasikuttan A.C. Cucurbituril-based supramolecular assemblies: prospective on drug delivery, sensing, separation, and catalytic applications. Langmuir, 2022, Vol. 38, no. 20, pp. 6249-6264.
  4. Chen H., Chan J.Y.W., Yang X., Wyman I.W., Macartney D.H., Bardelang D., Lee S.M.Y., Wang R. Developmental and organspecific toxicity of cucurbit[7]uril: In vivo study on zebrafish models. RSC Adv., 2015, Vol. 5, pp. 30067-30074.
  5. Das D., Assaf K.I., Nau W.M. Applications of cucurbiturils in medicinal chemistry and chemical biology. Front. Chem., 2019, Vol. 7, 619. doi: 10.3389/fchem.2019.00619.
  6. Hettiarachchi G., Nguyen D., Wu J., Lucas D., Ma D., Isaacs L., Briken V. Toxicology and drug delivery by cucurbit[n]uril type molecular containers. PLoS One, 2010, Vol. 5, no. 5, e10514. doi: 10.1371/journal.pone.0010514.
  7. Jeon Y.J., Kim S.Y., Ko Y.H., Sakamoto S., Yamaguchi K., Kim K. Novel molecular drug carrier: Encapsulation of oxaliplatin in cucurbit[7]uril and its effects on stability and reactivity of the drug. Org. Biomol. Chem., 2005, Vol. 3, pp. 2122-2125.
  8. Oun R., Floriano R.S., Isaacs L., Rowana E.G., Wheate N.J. The ex vivo neurotoxic, myotoxic and cardiotoxic activity of cucurbiturilbased macrocyclic drug delivery vehicles. Toxicol. Res., 2014, Vol. 3, pp. 447-455.
  9. Pashkina E., Aktanova A., Blinova E., Mirzaeva I., Kovalenko E., Knauer N., Ermakov A., Kozlov V. Evaluation of the immunosafety of cucurbit[n]uril on peripheral blood mononuclear cells In Vitro. Molecules, 2020, Vol. 25, no. 15, 3388. doi: 10.3390/molecules25153388.
  10. Pejchal J., Jošt P., Múčková L., Andrýs R., Lísa M., Zdarova Karasova J. A systematic evaluation of the cucurbit[7]uril pharmacokinetics and toxicity after a single dose and short-term repeated administration in mice. Arch. Toxicol., 2022, Vol. 96, no. 5, pp. 1411-1421.
  11. Pinchuk L.M., Filipov N.M. Differential effects of age on circulating and splenic leukocyte populations in C57BL/6 and BALB/c male mice. Immun. Ageing, 2008, Vol. 5, 1. doi: 10.1186/1742-4933-5-1.
  12. Uzunova V.D., Cullinane C., Brix K., Nau W.M., Day A.I. Toxicity of cucurbit[7]uril and cucurbit[8]uril: An exploratory in vitro and in vivo study. Org. Biomol. Chem., 2010, Vol. 8, pp. 2037-2042.

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2. Figure 1. The effect of cucurbiturils on relative number of neitrophiles in the peripheral blood of laboratory animals

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