Репозиторий Университета

© 2019 Elsevier B.V. Brain delivery of drugs by nanoparticles is a promising strategy that could open up new possibilities for the chemotherapy of brain tumors. As demonstrated in previous studies, the loading of doxorubicin in poly(lactide-co-glycolide) nanoparticles coated with poloxamer 188 (Dox-PLGA) enabled the brain delivery of this cytostatic that normally cannot penetrate across the blood-brain barrier in free form. The Dox-PLGA nanoparticles produced a very considerable anti-tumor effect against the intracranial 101.8 glioblastoma in rats, thus representing a promising candidate for the chemotherapy of brain tumors that warrants clinical evaluation. The objective of the present study, therefore, was the optimization of the Dox-PLGA formulation and the development of a pilot scale manufacturing process. Optimization of the preparation procedure involved the alteration of the technological parameters such as replacement of the particle stabilizer PVA 30–70 kDa with a presumably safer low molecular mass PVA 9–10 kDa as well as the modification of the external emulsion medium and the homogenization conditions. The optimized procedure enabled an increase of the encapsulation efficiency from 66% to >90% and reduction of the nanoparticle size from 250 nm to 110 nm thus enabling the sterilization by membrane filtration. The pilot scale process was characterized by an excellent reproducibility with very low inter-batch variations. The in vitro hematotoxicity of the nanoparticles was negligible at therapeutically relevant concentrations. The anti-tumor efficacy of the optimized formulation and the ability of the nanoparticles to penetrate into the intracranial tumor and normal brain tissue were confirmed by in vivo experiments.

© 2018 Ehlers-Danlos syndrome (EDS) is a heritable connective tissue disorder characterized by skin hyperextensibility, abnormal wound healing, and joint hypermobility with prevalence 1:20 000. Its incidence is probably underestimated due to unknown number of subjects having mild symptoms who may have never been diagnosed through entire life time. Classical EDS is characterized by pathogenic variants of genes encoding type V collagen. The biological effects and health risks of patients with EDS exposure to low doses of ionizing radiation is poorly understood. The aim of this study was to investigate biological effect of low doses of ionizing radiation in children with EDS. Background values of chromosome aberrations in children suffering from classical EDS were determined and compared with control subjects. The in vitro experiment was performed by γ-irradiation of blood lymphocytes from EDS patients and healthy subjects at low doses (0.1, 0.2 and 0.3 Gy). Results show a significant increase level of spontaneous and radiation-induced chromosomal aberrations in children suffering from EDS in comparison with the control subjects (p < 0.05). In conclusion, children with EDS express higher background chromosome aberration frequency and increased radiosensitivity. These findings suggest specific susceptibility of EDS patients and importance of future investigation on risks of diagnostics and therapy which include radiation and genotoxic agents.

© 2018, Media Sfera. All rights reserved. The article describes a newly developed and tested diffractive optical element (DOE) that converts non-uniform radiation of the laser output into a homogeneous ring. The Gerchberg-Saxton algorithm is shown to be well suited for achieving annular intensity distribution. Testing this ring transducer on threshold-plasticity cornea demonstrated the reversibility of axisymmetric changes in the cornea. Atomic-Force microscopy of the area of maximum stresses in the corneal periphery showed no significant changes in the structure of the cornea when irradiated in the selected mode. Measurement of Young’s modulus of the corneal surface areas after their irradiation also revealed no changes in the elastic properties, while examination of the corneal structure demonstrated the absence of significant structural changes in irradiated samples compared with intact ones.

© 2018 Copyright SPIE. The paper presents the results of the studies of influence of optical radiation with wavelengths of 520 and 780 nm on human glial cells (U251) at the range of exposure times ∼ 1-15 min. It was found that after the first minute of irradiation at the wavelength of 780 nm, the relative number of apoptotic cells significantly increased. The result corroborates the concept of biological hazard of optical radiation for tumor cells, and suggests that the approach has a great potential in clinical application for the treatment of human glioma.