ON THE POSSIBLE USE OF EXOGENOUS HISTONES AND CATIONIC PEPTIDES IN MOLECULAR BIOTECHNOLOGY

DOI: https://doi.org/10.29296/24999490-2020-02-01

A.D. Nozdrachev(1, )2, O.A. Goryukhina(2), S.V. Martyushin(3), I.V. Mishchenko(2) 1-Pavlov Institute of Physiology, Russian Academy of Sciences, Naberezhnaya Makarova, 6, Saint-Petersburg, 199034, Russian Federation; 2-St.Petersburg State University, Universitetskaya Naberezhnaya 7–9, Saint-Petersburg, 199034, Russian Federation; 3-State Research Institute of Highly Pure Biopreparations, Pudozhskaya, 7, Saint-Petersburg, 197110, Russian Federation E-mail: [email protected]

The prospect of developing transport systems using histones for delivery of therapeutic agents possessing poor penetration characteristics through cellular membranes and tissue barriers has been investigated. A review of the literary, as well as proper data, are presented concerning of mucoadhesive protein therapeutic agents. Delivery systems have been designed to obtain entrapment of protein therapeutic agents into nanoshperes during nanosphere preparation from dextran. Such mucoadhesive delivery systems containing histones immobilized on nanospheres for site-specific delivery of protein therapeutic agents to target (organ or tissue) for intranasal delivery. An increase in the mucoadhesive properties of dextran nanospheres with diameter of 100–200 nm coated by histones is due to electrostatic interaction of positively charged histones with negatively charged mucins of sialic acid, which leads to the formation of mucus layer and nanospheres associations over a long period of time. Moreover, the release of protein during nanospheres resorption can occur in mucus layer due to the fact that the protein will be absorbed paracellular or transcellular in the underlying epithelium of the mucous membrane. Further protein intake can be carried out along the olfactory epithelial route by means of axoplasmic transport along of olfactory neurons into the olfactory bulbs and from them using neuronal pathways in central nervous system. Histones immobilized on nanospheres can also be used to modify surfaces intended for cell cultivation. They can be applied as components to three-dimensional pore matrices that are designed for producing tissue-like structures in vitro.
Keywords: 
blood-brain barrier, exogenous histones, cationic peptides, mucoadhesive protein therapeutic agents delivery system, dextran nanospheres, intranasal delivery

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