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. 2021 Dec 31;12(1):148.
doi: 10.3390/nano12010148.

Preparation and Characterization of a Glycyrrhizic Acid-Based Drug Delivery System for Allergen-Specific Immunotherapy

Ekaterina Pashkina  1 , Veronika Evseenko  2 , Natalya Dumchenko  3 , Maxim Zelikman  2 , Alina Aktanova  1 , Maria Bykova  4 , Mikhail Khvostov  5 , Aleksandr Dushkin  2 , Vladimir Kozlov  1
Affiliations

Preparation and Characterization of a Glycyrrhizic Acid-Based Drug Delivery System for Allergen-Specific Immunotherapy

Ekaterina Pashkina et al. Nanomaterials (Basel). .

Abstract

The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to the mucosa, various delivery systems, such as liposomes, dendrimers, nanoparticles, etc., can be used. To date, there are data on the creation of delivery systems based on glycyrrhizic acid (GA) and its derivatives, but such a delivery system has not been used for allergen-specific therapy until now. It is also known that GA has an anti-inflammatory effect, shifts the balance towards Th1, and increases the number of Treg cells, meaning that it could potentially enhance the anti-allergic effect of AIT and reduce the risk of unwanted side effects. Thus, the study of the immunomodulatory effect of the supramolecular complexes (micelles) of GA with extracts of allergens holds promise for the development of new drugs for AIT.

Keywords: allergen-specific immunotherapy; drug delivery; glycyrrhizic acid; house dust mite.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Measurement of particle size in solution by light scattering. We studied aqueous solutions of peptide 10 μg/L (blue curves), GA 100 μg/L (red curves), and a solution obtained by mixing two previous solutions 1:1 (green curves). In each solution, measurements were carried out twice: 1–5 h after preparation (solid line), and one day after preparation (dashed line). All distributions on the graph are normalized. The measurement results show the presence of several sizes of associates in solutions.
Figure 2
Figure 2
Effects of GA and Der p 1 on cell viability of different cell cultures. (a) effects of the GA on cell viability of RPMI-2650 cells. (b) effects of the GA on cell viability of B16 cells. (c) effects of the GA on cell viability of PBMCs. (d) effects of the Der p 1 and Der p 1–GA mixture on cell viability of PBMCs. * Indicates a significant difference (p < 0.05); ** indicates a significant difference (p < 0.01); *** indicates a significant difference (p < 0.001); **** indicates a significant difference (p < 0.0001).
Figure 3
Figure 3
Evaluation of the permeability of Der p 1 across the RPMI-2650 monolayer.
Figure 4
Figure 4
T cell subsets after cultivation with GA–Der p 1 mixture. Data are presented as box-and-whisker plots, with boxes extending from the 25th to the 75th percentile, with a horizontal line at the median, while the whiskers extend to the lowest and highest data points (n = 10). * Indicates a significant difference (p < 0.05) vs. control.
Figure 5
Figure 5
CD4+ cell subsets after cultivation with GA–Der p 1 mixture. Data are presented as box-and-whisker plots, with boxes extending from the 25th to the 75th percentile, with a horizontal line at the median, while the whiskers extend to the lowest and highest data points (n = 10).
Figure 6
Figure 6
The relative number of CD3+ cells after cultivation with GA–Der p 1 complex. Data are presented as box-and-whisker plots, with boxes extending from the 25th to the 75th percentile, with a horizontal line at the median, while the whiskers extend to the lowest and highest data points (n = 10); ** indicates a significant difference (p < 0.01); *** indicates a significant difference (p < 0.001).
Figure 7
Figure 7
Spontaneous cytokine production by PBMCs cultured in the presence of the GA–Der p 1 complex or its components. Data are presented as box-and-whisker plots, with boxes extending from the 25th to the 75th percentile, with a horizontal line at the median, while the whiskers extend to the lowest and highest data points (n = 7); * Indicates a significant difference (p < 0.05).
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