In this work, the biomedical applicability and physical properties of magnesium-based metallic glass/polycaprolactone (PCL) composites are explored. The composites were fabricated via mechanical alloying and subsequent coextrusion. The coextrusion process was carried out at a temperature near to the supercooled liquid region of the metallic glass and the viscous region of the polymer. The structures, as well as thermal and mechanical properties of the obtained samples were characterized, and in vivo investigations were undertaken. The composite samples possess acceptable thermal and mechanical properties. Tensile tests indicate the ability of the composites to withstand more than 100% deformation. In vivo studies reveal that the composites are biologically compatible and could be promising for biomedical applications.

Doxorubicin is a well-known antitumor drug that is not employed for chemotherapy of brain tumors. Indeed, doxorubicin does not penetrate across the blood-brain barrier in therapeutic concentrations. To study the antitumor effect of doxorubicin combined with nitrosorbide on intracranial experimental glioblastoma 101/8 in rats. Male Wistar rats (n=86) with intracranial implanted glioblastoma 101/8 received doxorubicin (i.v. 1.5 mg/kg thrice) alone or in combination with nitrosorbide (i.v or orally, 0.5 mg/kg thrice) in 2, 5 and 8 days after implantation. Efficacy was assessed considering survival and brain tumor volume in 14 days after tumor implantation. Combination of doxorubicin and nitrosorbide significantly increased survival (57% and 155%, respectively) and slowed down tumor growth (16±12 and 8±6 mm³, respectively) compared to doxorubicin alone. Effectiveness of nitrosorbide alone was trivial. Nitric oxide donor nitrosorbide considerably potentiated the antitumor effect of doxorubicin against intracranial 101/8 glioblastoma in rats.

Introduction. Doxorubicin (Dox) in the composition of poly(lactic-co-glycolic acid, 50:50) (PLGA) – nanoparticles has high antitumor efficacy in rats with glioblastoma 101.8. However, the toxic effect of Dox-PLGA is not well understood. The aim of the study was morphological and biochemical evaluation of the hepatotoxic and cardiotoxic effects of doxorubicin and Dox-PLGA in the glioblastoma 101.8 treat-ment in Wistar rats. Materials and methods. The study was performed on 24 male Wistar rats with glioblastoma: no treatment (n=7), treated with doxorubicin (n=9) or Dox-PLGA (n=8) intravenously at a dose of 1.5 mg/kg on days 2, 5 and 8 after tumor implantation. On the 14th day of the experiment, morphological changes in the myocardium and liver were examined. Hematological and biochemical blood tests were performed. Results.When treating rats with experimental glioblastoma 101.8, Dox-PLGA in comparison with doxorubicin has less pronounced cardiotoxic and hepatotoxic effects according to the morphological, hematological and biochemical tests. Inflammatory changes in the myocardium of the animals treated with Dox-PLGA were less pronounced and widespread than the ones treated with doxorubicin. The activities of total and cardiac creatine phosphokinase (CPK) isoforms and AST were statistically significantly lower in Dox-PLGA group than in animals with glioblastoma without treatment and receiving doxorubicin. The hepatotoxic effects of Dox-PLGA were minimal. Unlike animals treated with doxorubicin, they had mild hepatocyte dystrophy. ALT activity in all groups did not differ from the reference values. Conclusion. Compared with doxorubicin, the nanosomal form of Dox-PLGA in the experimental glioblas-toma 101.8 treatment has less pronounced cardio- and hepatotoxic effects. Keywords: rat glioblastoma 101.8, doxorubicin, PLGA-nanoparticles, toxic effect, liver, myocardium, morphology, biochemistry

Hyaluronic acid (HA), a major glycosaminoglycan of the brain extracellular matrix, modulates cell behaviors through binding its receptor, Cd44. In this study, we assessed the influence of HA on high-grade brain tumors in vitro. The model comprised cell cultures derived from six rodent carcinogen-induced brain tumors, forming 3D spheroids prone to spontaneous fusion. Supplementation of the standard culture medium with 0.25% HA significantly inhibited the fusion rates, preserving the shape and size uniformity of spheroids. The 3D cultures were assigned to two groups; a Cd44lo group had a tenfold decreased relative expression of Cd44 than another (Cd44hi) group. In addition, these two groups differed by expression levels of Sox2 transcription factor; the correlation analysis revealed a tight negative association for Cd44 and Sox2. Transcriptomic responses of spheroids to HA exposure also depended on Cd44 expression levels, from subtle in Cd44lo to more pronounced and specific in Cd44hi, involving cell cycle progression, PI3K/AKT/mTOR pathway activation, and multidrug resistance genes. The potential HA-induced increase in brain tumor 3D models’ resistance to anticancer drug therapy should be taken into account when designing preclinical studies using HA scaffold-based models. The property of HA to prevent the fusion of brain-derived spheroids can be employed in CNS regenerative medicine and experimental oncology to ensure the production of uniform, controllably fusing neurospheres when creating more accurate in vitro brain models.