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Gene therapy is one of the most promising approaches in regenerative medicine. Gene-activated matrices provide stable gene expression and the production of osteogenic proteins in situ to stimulate osteogenesis and bone repair. In this study, we developed new gene-activated matrices based on polylactide granules (PLA) impregnated with BMP2 polyplexes and included in chitosan hydrogel or PRP-based fibrin hydrogel. The matrices showed high biocompatibility both in vitro with mesenchymal stem cells and in vivo when implanted intramuscularly in rats. The use of porous PLA granules allowed the inclusion of a high concentration of polyplexes, and the introduction of the granules into hydrogel provided the gradual release of the plasmid constructs. All gene-activated matrices showed transfecting ability and ensured long-term gene expression and the production of target proteins in vitro. At the same time, the achieved concentration of BMP-2 was sufficient to induce osteogenic differentiation of MSCs. When implanted into critical-size calvarial defects in rats, all matrices with BMP2 polyplexes led to new bone formation. The most significant effect on osteoinduction was observed for the PLA/PRP matrices. Thus, the developed gene-activated matrices were shown to be safe and effective osteoplastic materials. PLA granules and PRP-based fibrin hydrogel containing BMP2 polyplexes were shown to be the most promising for future applications in bone regeneration.

The pharmacokinetics and bioavailability of a derivative of 3,7-diazabicyclo[3.3.1]nonane exhibiting a nootropic effect, were studied after a single dose to rats. The pharmacokinetics of the compound was studied after oral and intravenous administration to 270 male rats Sprague Dawley at doses of 2.5 mg/kg, 13 mg/kg and 25 mg/kg. Its distribution in organs and tissues (brain, thymus, heart, lungs, liver, kidneys, and spleen) was also investigated. It was found that after a single intravenous administration, the investigated substance was determined in the blood of animals for 24 h; the half-life was 4.69 h. The relative bioavailability of the 3,7-diazabicyclo[3.3.1]nonane derivative after oral administration was 42.3%, thus suggesting the prospect of creating dosage forms for oral administration. After a single oral administration, the dose dependence of AUC0-t was exponential. The substance is characterized by heterogeneous distribution in the body with preferential accumulation mainly in well-vascularized tissues.Issledovana farmakokinetika i biodostupnost' veshchestva, iavliaiushchegosia po khimicheskoĭ strukture proizvodnym 3,7-diazabitsiklo[3.3.1]nonana, pokazavshego v éksperimente nootropnoe deĭstvie, pri odnokratnom vvedenii u krys. Farmakokinetika izuchalas' pri peroral'nom vvedenii atravmaticheskim zondom i vnutrivennom vvedenii 270 krysam-samtsam linii Sprague Dawley v dozakh 2,5 mg/kg, 13 mg/kg i 25 mg/kg. Takzhe provodilos' izuchenie raspredeleniia étogo veshchestva v organakh i tkaniakh (mozg, timus, serdtse, legkie, pechen', pochki, selezenka). Ustanovleno, chto posle odnokratnogo vnutrivennogo vvedeniia veshchestvo opredeliaetsia v krovi zhivotnykh na protiazhenii 24 ch; period poluvyvedeniia sostavil 4,69 ch. Otnositel'naia biodostupnost' proizvodnogo 3,7-diazabitsiklo[3.3.1]nonana pri peroral'nom vvedenii sostavila 42,3%, chto govorit o perspektive sozdaniia lekarstvennykh sredstv dlia priema vnutr'. Pri odnokratnom peroral'nom vvedenii zavisimost' AUC0-t ot dozy imeet éksponentsial'nyĭ kharakter. Raspredelenie v organizme neodnorodno, issleduemoe veshchestvo preimushchestvenno nakaplivaetsia v khorosho vaskuliarizirovannykh tkaniakh.

Articular cartilage is a highly organized tissue that has a limited ability to heal. Tissue engineering is actively exploited for joint tissue reconstruction in numerous cases of articular cartilage degeneration associated with trauma, arthrosis, rheumatoid arthritis, and osteoarthritis. However, the optimal scaffolds for cartilage repair are not yet identified. Here we have directly compared five various scaffolds, namely collagen-I membrane, collagen-II membrane, decellularized cartilage, a cellulose-based implant, and commercially available Chondro-Gide® (Geistlich Pharma AG, Wolhusen, Switzerland) collagen membrane. The scaffolds were implanted in osteochondral full-thickness defects, formed on adult Wistar rats using a hand-held cutter with a diameter of 2.0 mm and a depth of up to the subchondral bone. The congruence of the articular surface was almost fully restored by decellularized cartilage and collagen type II-based scaffold. The most vivid restoration was observed 4 months after the implantation. The formation of hyaline cartilage was not detected in any of the groups. Despite cellular infiltration into scaffolds being observed in each group except cellulose, neither chondrocytes nor chondro-progenitors were detected. We concluded that for restoration of hyaline cartilage, scaffolds have to be combined either with cellular therapy or morphogens promoting chondrogenic differentiation.

BACKGROUND: Parkinson's disease is one of the most common neurological diseases. Pathogenesis of the disease is associated with destruction and death of neurons that produce the neurotransmitter dopamine. The precursor to dopamine, which crosses the protective blood-brain barrier, is the amino acid 3, 4-dihydroxy-L-phenylalanine – levodopa, L-DOPA. The investigational drug is a pharmaceutical composition, containing L-DOPA as an active substance, which is distributed in a polymer matrix based on a biodegradable copolymer of lactic/glycolic acids. AIM: This work aimed to study the main pharmacokinetic parameters for the drug "L-DOPA – PC, nasal drops" and comparator drugs "L-DOPA in oil", "L-DOPA – PC in purified water", reference product – tablets "Madopar 125". METHODS: To increase the bioavailability of the active substance L-DOPA, a new route of administration was used for the first time – nasal administration. Pharmacokinetics of the innovative drug with the intranasal route of administration was investigated in rabbits. The L-DOPA concentration in blood plasma was determined by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). RESULTS: Bioavailability of the drug – nasal drops were 244.4% compared with the drug "Madopar 125". CONCLUSION: Assay procedure for the determination of L-DOPA in animal blood plasma using liquid chromatography with tandem mass-selective detection (HPLC-MS/MS) was developed and validated.