Experimental study of the allergenic potential of a drug based on hyaluronidase PEGylated using the technology of electron beam synthesis
Authors:   Novosibirsk State Medical University, Novosibirsk, Russia, Zabanova V.E. ,   Institute of Clinical and Experimental Lymphology, Branch of the Federal Research Center Institute of Cytology  and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, Ershov K.I. ,   Novosibirsk State Medical University, Novosibirsk, Russia; Institute of Clinical and Experimental Lymphology, Branch of the Federal Research Center Institute of Cytology  and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, Shvetsova A.M. ,   Institute of Clinical and Experimental Lymphology, Branch of the Federal Research Center Institute of Cytology  and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, Sherstoboev E.Yu. ,   Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk, Russia, Zhdanov V.V. ,   Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk, Russia, Drobysheva T.A. ,   Novosibirsk State Medical University, Novosibirsk, Russia, Fursova A.Zh. ,   Novosibirsk State Medical University, Novosibirsk, Russia; Institute of Clinical and Experimental Lymphology, Branch of the Federal Research Center Institute of Cytology  and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, Madonov P.G. ,   Novosibirsk State Medical University, Novosibirsk, Russia; Institute of Clinical and Experimental Lymphology, Branch of the Federal Research Center Institute of Cytology  and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
Published: July 2023

Introduction. Hyaluronidase is an enzyme preparation widely used in medicine, including ophthalmology. Hyaluronidase, having a protein structure, carries a potential danger in the form of undesirable allergic reactions. To avoid allergenic effects, protein structures are modified by combining with a polymer carrier, for example, by polyethylene glycol (PEG). Aim. To study the possible allergenic potential of hyaluronidase, PEGylated using the technology of electron beam synthesis, with various routes of administration. Materials and methods. The object of the study is PEGylated hyaluronidase (PEG-Hyal). Experimental animals are hybrid mice and guinea pigs. Seven types of experiments were carried out: anaphylactogenic activity; conjunctival challenge test; cutaneous applications; delayed-type hypersensitivity (DTH); active cutaneous anaphylaxis; indirect mast cell degranulation; inflammatory response to concanavalin A (ConA). Results. When studying anaphylactogenic activity, an anaphylactic reaction was not observed in guinea pigs. The conjunctival challenge test also revealed no signs of hypersensitivity to the drug. In the study of sensitization, no development of local allergic reactions was observed. In experiments to the study DTH in mice, there were no significant differences for the DTH index in the experimental and control groups. The assessment of active skin anaphylaxis has been showed that the diameter of the stained spot did not significantly differ in both experimental groups from the control one. In indirect mast cell degranulation experiments, it was found that there was no statistically significant change in the mast cell degranulation index. Evaluation of the allergenic potential of PEG-Hyal in the inflammatory response to ConA showed that there is no statistically significant difference between the experimental and control groups. Conclusion. Based on the results of the experiments, it can be concluded that PEG-Hyal does not have an allergenic potential in various routes of administration, which significantly expands the possibilities of its clinical use.