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

Abstract

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.