Polyethylene glycol (PEG) is one of the most versatile tools in pharmaceutics and biomedicine, combining high biocompatibility with a wide range of functional capabilities. The demand for PEG and its derivatives is steadily increasing due to the dynamic expansion of the biotechnology drug market and the development of personalized and targeted therapies. The paper considers the physicochemical properties of PEG and presents the systemized derivatives of the polymer. Particular attention is paid to the technology of protein PEGylation: the modification methods are analyzed, and the study demonstrates how this process alters the therapeutic and pharmacodynamic profiles of biopharmaceuticals. The review highlights the key areas of PEG application: fr om traditional use as a solvent and an excipient to cutting-edge solutions in targeted drug delivery and polymer matrices for regenerative medicine. An important part of the work is the analysis of the regulatory aspects governing the distribution of PEG-modified drugs, both within the international legal framework and within the Russian Federation. PEG is a revolutionary medical tool of the XXI century. In the modern paradigm, it is viewed not as a mere excipient but as a multifunctional, high-tech agent with proven clinical efficacy that provides an innovative approach to solving medical challenges.
The aim of the study was to evaluate the dynamics of endogenous somatostatin (SST) and its association with the intensity of 99mTc-Tektrotyd uptake and the cytokine profile in patients with primary anterior ST-segment elevation myocardial infarction during the early post-infarction period. Materials and Methods. The study included 22 patients admitted within the first 24 h from disease onset with a diagnosis of primary anterior ST-segment elevation myocardial infarction. The median age was 60.0 (53.0–65.5) years. All patients underwent percutaneous coronary intervention, echocardiography, and measurement of serum SST, high-sensitivity C-reactive protein, and interleukins (IL-1β, IL-6, IL-10) on days 1 and 5. On days 5–6, SPECT/CT with 99mTc-Tektrotyd was performed, with calculation of the maximum standardized uptake value of 99mTc-Tektrotyd (SUVmax) in the myocardium. Results. Myocardial 99mTc-Tektrotyd uptake was found in 18 patients (SUVmax — 2.8 [1.8–3.1] g/ml). The SST level on day 1 was 20.2 [11.2–40.8] pg/ml, and on day 5 — 23.2 [15.8–42.4] pg/ml (p=0.874); the dynamics were multidirectional. A negative correlation was found between SST concentration on day 1 and IL-1β level on day 1 (ρ=−0.645; p=0.001) and day 5 (ρ=−0.655; p=0.0001), as well as with left ventricular end-diastolic volume (ρ=−0.453; p=0.036) and the wall motion score index of the left ventricle (ρ=−0.484; p=0.023) on day 5. There was no correlation between SST level and SUVmax (ρ=−0.078; p=0.728). Regression analysis confirmed a significant effect of SST on IL-1β concentration (R2=0.526; p=0.0001 for day 1; R2=0.476; p=0.001 for day 5). Conclusion. In the early post-infarction period, endogenous SST demonstrates a negative relationship with the level of the proinflammatory cytokine IL-1β and left ventricular remodeling parameters, which emphasizes its important anti-inflammatory role. The absence of a direct association between SST concentration and SUVmax of 99mTc-Tektrotyd indicates the complex nature of peptide-receptor interaction and requires further investigation. The obtained data substantiate the potential of studying the somatostatinergic system as a promising therapeutic target in acute myocardial infarction.
The chemical structure of acridine contains ring-shaped nitrogen atoms, which determine its numerous biological and chemical properties. The scientific community considers the effects of acridine and its derivatives on tumors of various origins to be of particular interest. Numerous publications report the synthesis and study of new compounds in this group, some of which have been shown to be more effective than 5-fluorouracil and cisplatin. The aim of the study was to develop the liposomes based on pyrrolo[3,2-l]acridinone derivative Mob-155 S and study their antitumor activity regarding leukosis. Materials and Methods. Acridinone liposomes were prepared using a thin-film method followed by lyophilization. Lactose, mannose, and sucrose were dissolved in the dispersion as cryoprotectants prior to lyophilization. Spectrophotometry, dynamic light scattering, and electrophoresis were used to obtain the qualitative and quantitative characteristics of the liposomes. Stability of the samples was monitored at two temperature conditions (6–8°C and 21–23°C). Cytotoxic activity was determined on a Jurkat line in comparison with the native Mob-155 S substance and the liposomes without the active compound. Results. Immediately after production and during the short-term storage, Mob-155 S liposomes had the particles about 200 nm in size. After 40-day storage at 21–23°C, Mob-155 S concentration decreased, and there was an increase in the mean particle size up to 300–320 nm, and the polydispersity index up to 0.45–0.55. Experimental lyophilization with three types of saccharides was performed to improve stabilization. The marked protective effect manifested in the preservation of key quality liposome parameters was observed only under 10% mannose. In vitro studies demonstrated a significant reduction in tumor cell viability at relatively low concentrations of Mob-155 S.
The aim of the study was to produce polymer patches based on a mixture of regenerated silk fibroin (SF) and thermoplastic polyurethane (PU) with sirolimus (SRL) added, and study their surface structure, physical and mechanical properties and biocompatibility in vitro. Materials and Methods. Polymer patches were produced by electrospinning from a mixture of regenerated SF and thermoplastic PU dissolved in hexafluoroisopropanol in a weight ratio of 2:1 with simultaneously added SRL at concentrations of 0.175, 0.35, 0.525, and 0.7%. We studied the patch surface ultrastructure, physico-mechanical properties, and hemocompatibility; adhesive characteristics, cytotoxicity, and the effect of Ea.hy 926 endothelial cells on the proliferation. Results. The surface of the polymer patches had a porous-fibrous structure, with isolated areas of adhesions. The maximum porosity of the patches was 45.1%. The strength and rigidity of the SF-PU-SRL 0.175 and SF-PU-SRL 0.35 patches were higher than those of native arteries; all patches were more elastic than the mammary artery. The greatest mechanical conformity to native arteries was demonstrated by the SF-PU-SRL 0.525 and SF-PU-SRL 0.7 patches. The addition of SRL decreased the hydrophilicity of the patches compared to the SF-PU matrix. Contact of blood with the surface of the SF-PU-SRL patches provoked minimal hemolysis of erythrocytes and aggregation of platelets, which confirmed the optimal hemocompatibility of the patches. The adhesion of the patch surface was 4 times lower than that of the culture plastic, without a pronounced cytotoxic effect on Ea.hy 926 endothelial cells. The patches with a SRL content of 0.525% had the optimal antiproliferative effect. Conclusion. Due to the optimal surface porosity, the greatest correspondence of rigidity, strength and elasticity to native arteries, high hemocompatibility, low cytotoxicity and the achievement of an antiproliferative effect at a minimum concentration of SRL without a negative impact on the viability of endothelial cells, the polymer patch SF-PU-SRL 0.525 seems to be the most promising that enables to proceed to the assessment of its effectiveness in terms of preventing postoperative neointimal hyperplasia and restenosis in a model of arterial wall reconstruction.
Glioblastoma is a highly aggressive and currently incurable brain tumor. It is characterized by a pronounced immunosuppressive tumor microenvironment (TME), which limits the potential of any immunotherapy options. Targeted therapy with recombinant oncolytic viruses can modulate the properties of the TME, overcome the glioblastoma-mediated immunosuppression, and evoke an antitumor immune response. Recombinant vaccinia viruses are suitable for these tasks because they have a favorable safety profile and can be modified with cDNA of immunomodulatory factors for their expression in tumor cells. The aim of the study was to evaluate the impact of the recombinant vaccinia virus strain carrying the interleukin-15 cDNA (LIVP-mIL15) on the TME in the GL261 experimental glioma model. Materials and Methods. Using intravital fluorescence microscopy, in vivo bioluminescence imaging, brain magnetic resonance imaging, and flow cytometry of immune cell subpopulations, we evaluated the ability of the novel LIVP-mIL15 strains (LIVP-mIL15-RFP and LIVP-mIL15-FLuc) to affect GL261 glioma cells in 3D spheroids and in the syngeneic orthotopic GL261 glioma in C57BL/6 mice, as well as the dynamics of TME changes induced by immunotherapy. Results. The recombinant vaccinia virus strain LIVP-mIL15-RFP is capable of efficiently infecting GL261 glioma cells in 3D spheroids formed during cultivation in non-adherent plates and of inducing selective transgene expression in orthotopic glioma cells following a single stereotactic or intravenous administration. The bioluminescence signal of the recombinant vaccinia virus strain LIVP-mIL15-FLuc was detected in the tumor at 48, 72, and 144 h after stereotactic administration and at 72 h after intravenous virus administration. Stereotactic administration of LIVP-mIL15-RFP caused changes in the composition of immune cell subpopulations, with a relative increase in the proportion of IL-15-responsive NK cells and cytotoxic lymphocytes within the TME.
