This research focuses on the use of polymers and their derivatives in medicine and biotechnology.
The aim of this study was to characterize the physicochemical and biological properties of chitosan fragments and its complexes with various biologically active substances, as well as to determine the effect of a complex of modified polyvinylpyrrolidone with specific peptides on microorganisms, normal and tumor mammalian cell lines.
In the dissertation work the original method of obtaining chitosan from chitin of bee bodies and crabs' shells is developed, the conditions of its sterilization and storage are described. Significant heterogeneity of the obtained samples of chitosan from different sources, including industrial samples, was established.
Realized study the antimicrobial properties of chitosan against such strains as S. aureus, P. aeruginosa, E. coli, C. albicans. The high promise of chitosan as an antifungal drug, including against strains of C. albicans with multidrug resistance.
Decrease molecular weight chitosan causes increase its solubility, but at the same time it reduces the cytotoxic effects on yeast Candida albicans, and, conversely, chitosan fractions with higher molecular weight have higher antifungal activity.
The method of dissolving chitosan using glycolic acid was developed in the work, which allowed to obtain soluble samples of chitosan with high molecular weight at neutral pH.
An original method of obtaining a chitosan-melanin complex from bee stings has been developed. The activity of this complex against strains of C. albicans ATCC 885-655, and clinical isolate of C. albicans N12, with multidrug resistance to antifungal drugs was studied. The higher activity of the chitosan-melanin complex against strain N12 with multidrug resistance was demonstrated compared to that of chitosan. The death of yeast cells of C. albicans N12 upon contact with chitosan molecules was detected.
The low toxicity of this complex, as well as chitosan against mammalian cells at a dose of 0.2 mg / ml, including against normal human peripheral blood lymphocytes, has been shown, indicating its biocompatibility.
An original method for obtaining chitin from the fruiting bodies of basidiomycetes has been developed as another promising source for obtaining chitosan on an industrial scale. A spectral study of chitosan derived from fungi was performed.
A complex of chitosan crab with ethacridine lactate was created and the use of chitosan as a carrier of drugs was substantiated. The release of ethacridine lactate from its complex with chitosan was established, which ensured the prolongation of ethacridine lactate in the blood of experimental rats in comparison with free ethacridine lactate. The results indicate the possibility of prolonging the action of drugs in the bloodstream by conjugating them with chitosan.
Covalent conjugation of the monomeric form of the tripeptide Ser-Pro-Cis with polyvinylpyrrolidone derivatives was performed, which allowed to create conjugates with different biological activity. A screening study of these conjugates and selected the modification with the highest cytotoxic activity in vitro against malignant cells of the MCF7 and HCT116 lines at a dose of conjugate consisting of polymer (1.66 mg/ml) and covalently bound peptide (0, 13 mg/ml).
Inhibition of NK/Ly malignant lymphoma growth was observed in tumor-bearing mice of the C57/Black line at a cumulative dose of 30 mg/kg during in vivo administration of the conjugate. However, this complex compound has relatively low toxicity to pseudonormal cells of the HEK293 line of the human kidney embryo and activated normal human peripheral blood lymphocytes.
It was found that the P4P conjugate with a FITC fluorescent label in the range of 2-6 h penetrates the cells of the MCF7 line of human breast cancer and accumulates in the vesicles of cells, but does not enter their nucleus.
An original approach has been developed to obtain target proteins of various factors using magnetic particles. Using MALDI-TOFF mass spectrometry was first identified intracellular proteins that interact with the complex P4P cells in mouse lymphoma NK / Ly and it can serve as molecular targets. Among the identified proteins are structural proteins of cells (actin, cytoskeleton keratin, cytoplasmic beta-actin, myosin) and serum albumin.
The results of the study of the P4P complex confirm the prospects of using modified polyvinylpyrrolidone derivatives for covalent conjugation with molecules of biological genesis to create new drugs. An important consequence of such modifications is an increase in the biological activity of the resulting conjugate.
