Biopolymer materials based on natural collagen (gelatin and hydrolyzed collagen) are widely used in the food, pharmaceutical and cosmetic industries due to their low toxicity, high biocompatibility, low antigenicity, and unique mechanical and technological properties. Hydrolyzed collagen, unlike gelatin, is formed by peptides with a lower molecular weight. It has higher bioavailability and biodegradability compared to gelatin. In this work, using low-temperature technologies, biopolymer matrices based on hydrolyzed collagen containing the antibacterial drug dioxidine were obtained. It has been shown that by varying such synthesis parameters such as the concentration of hydrolyzed collagen in the precursor solution (from 1 to 10%), matrix cross-linking time (0.1-24 hours), cryoforming temperature (-30 and -196 °C) it is possible to change the morphology and structure matrix, its degradation time and drug release time. The composition and structure of dioxidine/hydrolyzed collagen systems were characterized by SEM, IR and UV spectroscopy. The antibacterial activity of the resulting dioxidine/hydrolyzed collagen systems against E. coli and S. aureus was characterized by the disk diffusion method.

Cryoforming of gelatin systems with the antibacterial drug dioxidine is carried out. The study considers the effect of systems’ synthesis conditions (gelatin concentration in the precursor solution) on their structural characteristics, antibacterial activity, and drug release time. The composition and structure of the dioxidine/gelatin and dioxidine/hydrolyzed collagen systems are characterized by SEM, IR, and UV spectroscopy. The disk diffusion method is used to determine the antibacterial activity of the obtained systems against E. coli and S. aureus .

Cryochemical modification methods are used to obtain hybrid composites of the antibacterial drug gentamicin sulfate, as well as copper and iron nanoparticles, which are promising precursors of the targeted drug delivery systems. The resulting systems are antibiotic nanoparticles of 50 to 300 nm, including copper and iron nanoparticles of 1 to 20 nm (according to the results of physicochemical analysis by IR spectroscopy, X-ray diffraction analysis, dynamic light scattering, and scanning and transmission microscopy). The composites obtained showed higher antibacterial activity againstE. coli,P. aeruginosa, andB. cereuscompared to the individual components.

Cryochemical nanotechnologies are used to obtain hybrid systems comprising the antibacterial drug dioxidine, metal (Ag, Cu) nanoparticles, and biopolymer matrices (cryogels) based on gelatin, potassium alginate, and chitosan. Data from IR, UV, and NMR spectroscopy, plus TEM and SEM microscopy, show the resulting systems consist of wide-porosity matrices (pore diameters, 10–200 μm) that contain antibacterial drugs and nanoparticles of silver (2–30 nm) or copper (1–5 nm). It is found these systems ensure a gradual release of dioxidine (40 min to 3 days, depending on the nature of the matrix). The high activity of hybrid composites based on metals and dioxidine incorporated into biopolymer cryostructurates against the growth of E. coli 52 and S. aureus 144 is estimated, relative to the individual components in the same matrices.

Using the method of cryochemical synthesis, systems of prolonged release of gentamicin sulfate modified with silver (2–30 nm) and copper (1–9 nm) nanoparticles from cryostructured biopolymer matrices based on gelatin with a pore size of 10‒50 μm are obtained. The composition and structure of the systems are confirmed by the data of IR, UV, and NMR spectroscopy; TEM; SEM; and thermoanalytical methods of analysis, and the rate of release of the drug is determined by conductometry. Hybrid composites based on metals and gentamicin sulfate showed greater activity in suppressing the growth of E. coli 52 and S. aureus 144 than their components separately.

Методом криохимического синтеза получены системы пролонгированного высвобождения гентамицина сульфата, модифицированного наночастицами серебра (2–30 нм) и меди (1–9 нм) из криоструктурированных биополимерных матриц на основе желатина с размером пор 10–50 мкм. Состав и структура полученных систем подтверждены данными ИК-, УФ-, ЯМР-спектроскопии, ПЭМ, СЭМ, термоаналитических методов анализа, скорость высвобождения лекарственного препарата определена кондуктометрически. Гибридные композиты на основе металлов и гентамицина сульфата показали большую активность к подавлению роста E. coli 52 и S. aureus 144 , чем их составляющие по отдельности.

Cryochemical approaches have been used to synthesize hybrid systems consisting of a cryomodified β form of dioxydine (particle size of 30‒350 nm) and silver or copper nanoparticles (average size of 5‒18 nm). These hybrid composites and their precursors are incorporated into biopolymer cryostructures based on gelatin and calcium alginate. Hybrid composites based on metals and antibacterial drugs are very active in the inhibition of growth of E. coli 52, S. aureus 144, and M. cyaneum 98 in comparison with their separate components.

Криохимические подходы использованы для синтеза гибридных систем, представляющих собой криомодифицированную β-форму диоксидина (частицы размером 30–350 нм), содержащую наночастицы серебра или меди (со средним размером 5–18 нм). Полученные гибридные композиты и их прекурсоры были включены в биополимерные криоструктуры на основе желатина и альгината кальция. Гибридные композиты на основе металлов и антибактериальных препаратов проявляют большую активность к подавлению роста E. coli 52, S. aureus 144 и M. cyaneum 98, чем их составляющие по отдельности.

Cryochemical synthesis of hybrid nanocomposites based on the antibacterial drug, dioxidine, and metals (Ag, Cu) was performed. According to the data of H1 NMR, UV, and IR spectroscopy, low-temperature argon sorption, and transmission electron microscopy, met-als in these systems exist as Ag nanoparticles (with dimensions of 2—30 nm) or Cu nanoparti-cles (10—40 nm) involved in the bigger-sized particles of dioxidine with dimensions of 50—350 nm. These hybrid nanocomposites show the enhanced antibacterial activity towards the microbial cells Escherichia coli 52, Staphylococcus aureus 144, Mycobacterium cyaneum 98. The as-prepared drug nanocomposites are incorporated into spongy alginate cryostructurates. The feasibility of drug release from the biopolymer alginate carrier is proved and the related antibacterial activity is demonstrated.

Dioxidine nanoparticles are prepared via cryochemical modification of the pharmacopoeial dioxidine substance. The form of the cryomodified dioxidine is characterized by data from 1 H NMR spectroscopy; X-ray diffraction analysis; such thermal analytical methods as TG and DSC; low-temperature argon adsorption; and transmission electron microscopy. It is shown that the cryomodified samples are synthesized in the form of dioxidine nanocrystals 50–300 nm in size, with a crystal structure differing from that of the initial pharmacopoeial substance. The prepared cryomodified dioxidine nanoparticles inhibit the growth of E. coli 52, S. aureus 144, M. cyaneum 98 , and B. cereus 9 better than the initial pharmacopoeial substance, and have comparable chronic toxicity.

Hybrid nanocomposites consisting of an antibacterial drug, dioxidine, and copper nanoparticles are obtained by cryochemical synthesis. It is shown by UV spectroscopy, X-ray diffraction, PAM, and low temperature argon adsorption that the obtained hybrid systems represent dioxidine particles with a size of 100 to 400 nm, including copper particles with the size of 50 to 150 nm. The resulting composites possessed higher antibacterial activity against E. coli 52 than the initial dioxidine and copper nanoparticles.

One way to increase bioavailability and efficiency of drug substances is to decrease their particles up to nanoscale level and to change their crystal structure. A new stable nanoscale form of a polymorphic antibacterial 2,3-bis-(hydroxymethyl)-quinoxaline-N,N′-dioxyde (dioxidine) modification characterized with a gas chromatography, NMR, XRF, TEM, and thermoanalytic methods (TG, DTG, DSC) was obtained via cryochemical synthesis. The new polymorphic dioxidine modification was proved to be more active in growth inhibition processes of gram-positive M. cyaneum 98 and gram-negative E. coli bacterial strains than officinal modification.