Аннотация:Current studies based on the technology "NanoZYME" are directed to the creation of enzyme-containing polymer nano-systems intended for the treatment of several diseases (diseases of the central nervous system, brain, neurotoxic injury, eye inflammations, bacterial infections).
With the use of "NanoZYME" technology based on organophosphate hydrolase enzyme (OPH), series of original biomaterials (hydrolytic nanozyme) that catalyze the decomposition of organophosphorus compounds (POS) were developed. The nanoformulation effect on chemical warfare agents and pesticides was studied in vivo using different ways of administration into the body: intravenously, intramuscularly, intraperitoneally and buccally.
As revealed, it is possible to use these formulations as effective antidotes in cases of intoxication by high concentrations organophosphorus agents (up 6xLD50), survival rate is 100%. It was also demonstrated for the first time ever that it is possible to use these formulations as protectants (the same 100% survival rate), if they are administrated into the body a few hours (from 2 to 15 h) prior to intoxication by high-dose of organophosphorus agents (up 8xLD50). The hydrolytic nanozyme samples can be stored up to 500 days at room temperature without losing the enzyme activity. The absence of cytotoxicity and immunogenicity was shown. As found, the dosage of these formulations can be lowered be dozens of times comparing to the conventional antidotes used worldwide.
The properties and new formulations composed of SOD-containing polymeric nano complexes and conjugates were investigated. Significant improvement in the course of the disease of immunogenic uveitis (an inflammatory disease of the eye) at a local drip containing superoxide dismutase (SOD1-nanozyme) nanozyme solutions, in the eyes of rabbits was shown. Histological studies have proved the clinical and biochemical data. These results demonstrate high potential therapeutic efficacy of SOD1 nanozyme to treat a wide range of inflammatory diseases in the eye.
Nanoparticles of SOD1-polycation are safe in terms of survival rate for animals with spinal cord injury, and their administration improves recovery dynamics of rat’s voluntary movements. Novel bionanomaterials based on nanoparticles bilayer composition SOD1-polycation-polyanion were developed. Significant increase of the yield of incorporation of the protein (from 20% to 70%) and the efficiency of the enzyme (up to 70%) were observed together with drug cytotoxicity reduction.
Bacteriolytic nanozymes effective against Gram-positive and Gram-negative bacteria were prepared and used as antibacterial agents. As an example, nanocompositions of enzymes from bacteriophage phi 11 and K with block-copolymers, effectively lysing of antibiotic resistant strains of Staphylococcus aureus, having high stability and decreased (2-10 times) toxicity, were investigated and characterized.