Levofloxacin (LFX) is a highly effective anti-tuberculosis drug with a pronounced bactericidal activity against Mycobacterium tuberculosis (Mtb). In this work, an “organic solvent-free” approach has been used for the development of polylactic-co-glycolic acid (PLGA) microparticles and scaffolds containing LFX at a therapeutically significant concentration, providing for its sustained release. To achieve the target, both nonpolar supercritical carbon dioxide and polar supercritical trifluoromethane have been used. By changing the composition, surface morphology, size, and internal structure of the polymer carriers, one can control the kinetics of the LFX release into phosphate buffered saline solutions and physiological media, providing for its acceptable burst and desirable concentration in the prolonged phase. The biocompatibility and bactericidal efficacy of PLGA/LFX carriers assessed both in vitro (against Mtb phagocytosed by macrophages) and in vivo (against inbred BALB/c mice aerogenically infected with Mtb) demonstrated their anti-tuberculosis activity comparable with that of the standard daily intragastric levofloxacin administration. These results make it possible to consider the developed compositions as a promising candidate for anti-tuberculosis control release formulations providing for the further evaluation of their activity against Mtb and their metabolism in vivo over long periods of tuberculosis infection.

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.

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.

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 e

Micronization of the pharmaceutical substance levofloxacin hemihydrate (LFC) was studied by the RESS method with trifluoromethane (CHF₃) as a polar supercritical solvent. Scanning electron microscopy showed that, at a CHF₃ temperature of 50°C, particles of micronized LFC have the shape of microgranules of submicron size. At a temperature of 100°C, the particles take the shape of thin (less than 0.1-μm-thick) elongated plates with rounded edges. At this temperature, an increase in the CHF₃ pressure from 20 to 35 MPa leads to an increase in the average particle size from 1 to 2 μm, respectively. X-ray powder diffraction analysis of samples obtained at a temperature of 50°C determined the identity of the original and micronized LFC substances, which correspond to the structure of levofloxacin hemihydrate C₃₆H₄₀F₂N₆O₈⋅H₂O. An increase in the process temperature to 100°C leads to the formation of one of pseudopolymorphs of levofloxacin—levofloxacin monohydrate C₁₈H₂₀F₂N₃O₄⋅H₂O—in the micronized LFC.