E. N. Antonov

A Study of ibuprofen solubility in supercritical carbon dioxide by Fourier-transform infrared spectroscopy

In the work, a method of study of solubility of pharmaceutical substances in high-pressure gases and supercritical media with Fourier-transform IR spectroscopy has been developed. An investigation of the process of ibuprofen dissolution in supercritical carbon dioxide (SC CO2) in a real-time scale has been performed. On the basis of analysis of the time dependences of the integral intensities of the selected IR-absorption bands of ibuprofen on the value of the initial weighed portion the value of solubility (molar fraction) of ibuprofen in SC CO2 at a temperature of 35°C and pressure of 15.0 MPa was obtained, being equal to (8.9 ± 1.6) × 10−3.

Selective Laser Sintering of Bioactive Composite Matrices for Bone Tissue Engineering

A method for surface-selective laser sintering which produces mineral-polymeric materials based on calcium phosphates and aliphatic polyesters was developed. Three-dimensional matrices of the given architectonics for replacement of bone defects and bone tissue engineering were obtained. The microstructure of the experimental samples obtained and their surface morphology and internal structure were investigated by scanning electron microscopy (SEM). The characteristic values of the compressive strength and relative deformation of the mineral-polymer composite samples obtained by surface-selective laser sintering of fine powders consisting of 80 wt % ceramic granules based on tricalcium phosphate and 20 wt % D,L-polylactide PDL04 corresponded to the characteristic indices of the similar parameters for the trabecular bone tissue. As a result of the initial study of the biological properties of mineral-polymer composite scaffolds made by surface-selective laser sintering, it was shown that they had low cytotoxicity and no adverse effects on the proliferative potential of mesenchymal stem cells. The technology of surface-selective laser sintering suggested could be effectively used to create scaffolds for bone tissue engineering.

Solubility of Acizol in supercritical carbon dioxide

The dissolution of the Acizol® pharmaceutical substance (bis(1-vinylimidazole-N) zinc diacetate) in supercritical carbon dioxide (SC-CO2) has been studied by the Fourier transform infrared spectroscopy (FTIR). The molar fraction of acizol in a saturated solution in carbon dioxide at a temperature of 40°C and pressure of 10.0 MPa has been determined to be (4.9 ± 1.3) × 10−3, based on the analysis of the temporal dependences of the integral intensities of the IR absorption analytical band (1 650 cm−1) of acizol on the value of its initial weight.

New “old” polylactides for tissue engineering constructions

New methods for the synthesis of aliphatic polyesters were proposed and realized with highly effective and low-toxic 1,5,7-triazabicyclo[4.4.0]decene-5 and (2,6-di-tert-butyl-4-methylphenoxy)-butyl-magnesium as catalysts and ethanol as an initiator. The interaction processes between D,L-polylactides of different molecular weights, obtained through these methods, and supercritical carbon dioxide were studied to provide “soft and dry” formation (without high temperatures and toxic organic solvents) of highly porous (up to 90 vol %) bioresorbable matrices for tissue engineering constructions. The chemical structure, molecular weight characteristics, morphology, cytotoxicity, and matrix properties of the samples synthesized from D,L-polylactides were studied with nuclear magnetic resonance spectroscopy, gel permeation chromatography, scanning electron microscopy, colorimetric testing to estimate the metabolic activity of cells (MTT test), and coloration with a vital fluorescent dye of in vitro cultures of multipotent stromal cells of human adipose tissue. A comparative analysis for biocompatibility of these matrices with control samples made from “medical grade” polylactide analog produced industrially indicates that the materials developed can be recommended for tissue engineering.

Thermochemical gypsum conversion forming calcium phosphates

A study was carried out on effect of the conditions of physicochemical conversion of a porous gypsum intermediate product to calcium phosphates. Depending on the initial conditions of sample preparation, the materials around hydroxyapatite and dicalcium phosphate were obtained. The conducted thermal analysis and dilatometric studies made it possible to propose the conditions of thermal treatment preventing shrinkage and deformation of samples. After thermal treatment at 1000°C, fine crystalline porous materials were obtained with crystal size between 0.5 and 2 μm and pore size up to 50 μm on the basis of β-tricalcium phosphate with strength up to 2.8 MPa. The developed pore structure and fairly high strength make it possible to use the developed materials based on tricalcium phosphate to obtain biomaterials for the replacement of defects in bone tissue.

Formation of a bioactive material for selective laser sintering from a mixture of powdered polylactide and nano-hydroxyapatite in supercritical carbon dioxide

Supercritical carbon dioxide (SC-CO2) is used to prepare bioactive composites from powdered polylactide and nanosized hydroxyapatite for surface-selective laser sintering of three-dimensional tissue engineering structures. The mixture of powdered polylactide and nanosized hydroxyapatite and cannot be directly laser-sinter because of the impossibility of forming continuous filaments from sintered polymer particles. The use of composite particles for sintering formed in SC-CO2 medium makes it possible to eliminate this shortcoming and to form continuous structures. Analysis of the composition and mechanical tests of such structures showed that the sintered composite obtained is fairly uniform, without destruction centers, capable of withstanding the same mechanical loads as the pure polymer, and therefore, suitable for use in tissue scaffold engineering.

Development of an HPLC-UV Method for Quantitative Determination of Acetylsalicylic Acid and Its Main Metabolite

An HPLC-UV method for determination of acetylsalicylic acid and its main metabolite, salicylic acid, in a model solution and in rabbit blood plasma was developed. Plasma samples were prepared by salting out. Chromatographic analysis was performed in isocratic mode over a Hypersil BDS C18 column using mobile phase MeCN—H2O (pH 2.5, 30:70) with detection at 230 nm. The limit of quantitation for acetylsalicylic and salicylic acids in the model solution was 0.05 μg/mL; in blood plasma, 0.2 μg/mL. The developed method was applied to the development of new acetylsalicylic-acid dosage forms based on biocompatible polymer carriers, including pharmacokinetic studies after i.m. implantation.

Model of the Destruction of Bioresorbable Polymers in Aqueous Media

The destruction of porous matrix polylactoglycolide (PLG) structures with different ratios of lactic and glycolic acids is experimentally studied in phosphate buffer saline. A mathematical model of this destruction that takes into account both the heterogeneous and autocatalytic hydrolysis of PLG as well as diffusion of their oligomers in the buffer solution and polymer free volume is developed. Gel-penetrating chromatography is used to analyze changes in the weight-average molecular weight of specimens studied and to determine the kinetic parameters of this process.

Fabrication of the Components for a Sustained-Release Injectable Dosage Form of Acetylsalicylic Acid Using Supercritical Carbon Dioxide

Fabrication of fine-grained (10–100 μm) bioresorbable powders of aliphatic polyesters containing therapeutically significant (up to 10 wt %) concentrations of acetylsalicylic acid using supercritical CO2 is studied. The process for fabricating the components of sustained-release injectable dosage forms of acetylsalicylic acid is elaborated. The kinetics of release of acetylsalicylic acid from polylactide microparticles into the normal saline solution in vitro is studied by high-performance liquid chromatography.

Visualization of Mesenchymal Stromal Cells in 2Dand 3D-Cultures by Scanning Electron Microscopy with Lanthanide Contrasting

Mesenchymal stromal cells from deciduous teeth in 2D- and 3D-cultures on culture plastic, silicate glass, porous polystyrene, and experimental polylactoglycolide matrices were visualized by scanning electron microscopy with lanthanide contrasting. Supravital staining of cell cultures with a lanthanide-based dye (neodymium chloride) preserved normal cell morphology and allowed assessment of the matrix properties of the carriers. The developed approach can be used for the development of biomaterials for tissue engineering.