In Vitro Human Blood-Brain Barrier Model for Drug Permeability Testing

Blood-brain barrier (BBB), although very important for protection of brain from major neurotoxins, negatively affects the treatment of central nervous system diseases by limiting the passage of neuropharmaceuticals from blood to the brain. Thus, researchers have to investigate the passage of the produced drug molecules through the BBB before they are introduced to the market. Although these experiments have been traditionally performed on experimental animals, drug permeability tests are now carried out mostly by in vitro BBB models due to ethical problems, differences between species, and expensive and troublesome in vivo test procedures. In this method, we explain how to model and characterize a realistic in vitro BBB model using human derived cells and perform a drug permeability test using this model.Scientific and Technological Research Council of Turkey (TUBITAK) [216M542, 116Z964]; Ege University Scientific Research Projects Council [16FBE003]; TUBITAK 2211-C Domestic Graduate Scholarship ProgramThis work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) [grant numbers 216M542 and 116Z964], TUBITAK 2211-C Domestic Graduate Scholarship Program, and Ege University Scientific Research Projects Council [grant number 16FBE003]. We thank Ege University Central Research Test and Analysis Laboratory Application and Research Center (EGE-MATAL), whose infrastructure we use for performing some parts of the protocol, and Bioengineer Mehmet Mert Celtikoglu, who contributed to the development of the protocol

Role of Intermediate Filaments in Blood-Brain Barrier in Health and Disease

The blood-brain barrier (BBB) is a highly selective cellular monolayer unique to the microvasculature of the central nervous system (CNS), and it mediates the communication of the CNS with the rest of the body by regulating the passage of molecules into the CNS microenvironment. Limitation of passage of substances through the BBB is mainly due to tight junctions (TJ) and adherens junctions (AJ) between brain microvascular endothelial cells. The importance of actin filaments and microtubules in establishing and maintaining TJs and AJs has been indicated; however, recent studies have shown that intermediate filaments are also important in the formation and function of cell-cell junctions. The most common intermediate filament protein in endothelial cells is vimentin. Vimentin plays a role in blood-brain barrier permeability in both cell-cell and cell-matrix interactions by affecting the actin and microtubule reorganization and by binding directly to VE-cadherin or integrin proteins. The BBB permeability increases due to the formation of stress fibers and the disruption of VE-cadherin interactions between two neighboring cells in various diseases, disrupting the fiber network of intermediate filament vimentin in different ways. Intermediate filaments may be long ignored key targets in regulation of BBB permeability in health and disease.EuroCellNet COST Action [CA15214]; Scientific and Technological Research Council of Turkey (TUBITAK) [216M542]The supports of EuroCellNet COST Action CA15214 and The Scientific and Technological Research Council of Turkey (TUBITAK) [grant number 216M542] are acknowledged

Implementation of Nanoparticles in Cancer Therapy

WOS: 000364531600019Cancer is a wide group of diseases and generally characterized by uncontrolled proliferation of cells whose metabolic activities are dtsrupted. Conventionally, chemotherapy, radiotherapy, and surgery are used in the treatment of cancer. However. in theory, even a sing/c cancer ce/I may trigger recurrence. The ref ore, these treatments cannot provide high survival rate for deadly types. Identijication of alternative methods in treatment of cancers is inevitable because of adverse effucts of con ventiona/methods. In the last few decades, nanotechnology developed by scientists working in different disciplines physics. chemistry, and biology offers great opportunities. It is providing elimination of both circulating tumor cei/.v and solid cancer cells by taryeting cancer cells. In this chaptem; inadequate parts of conventional treatment methods, nanoparlicie types used in new treatment methods of cancer. and targeting methods of nanopartic/es are summarized: furthermore, recommendations of future are provided

pH-Responsive Polymersome Microparticles as Smart Cyclodextrin-Releasing Agents

Bayir, Ece/0000-0003-4886-3860; Puglisi, Antonino/0000-0001-8998-0700WOS: 000490658900037PubMed: 31553586Cyclodextrins (CDs) are increasingly drawing attention as potential therapeutic tools in the treatment of cholesterol-associated diseases. However, bioavailability and delivery of CDs in the monomeric form still remain challenging. CD-based macromolecular systems seem to display a promising capacity in overcoming some of these limitations. Therefore, smart, stimuli-responsive nanosystems are currently being investigated in order to provide improved CD-releasing agents. Herein, we present a novel class of CD based polymersome microparticles (CD-PMs) designed for potential therapeutic use. A new synthetic route to obtain a CD-appended, pH-sensitive polymer that self-assembles into a stable polymersome microparticle is reported. Through an easy-to-use approach, a benzoic imine bond is incorporated into a poly(e-caprolactone) backbone and employed as a building block in the construction of the nanoarchitecture. the CD-PMs show cellular uptake representing a promising potential therapeutic tool in the treatment of cholesterol-associated conditions such as neurodegenerative diseases.European UnionEuropean Union (EU) [786560]This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement No. 786560. SEM and cell culture experiments were performed at EGE MATAL (Ege University/Izmir)

Optimization of bacterial cellulose production by Gluconacetobacter xylinus using carob and haricot bean

International Biomedical Engineering Congress -- 2015 -- Near E Univ, North Nicosia, CYPRUSWOS: 000380626900002PubMed ID: 26906562Bacterial cellulose (BC) can be used in medical, biomedical, electronic, food, and paper industries because of its unique properties distinguishing it from plant cellulose. BC production was statistically optimized by Gluconacetobacter xylinus strain using carob and haricot bean (CHb) medium. Eight parameters were evaluated by Plackett-Burman Design and significant three parameters were optimized by Central Composite Design. Optimal conditions for production of BC in static culture were found as: 2.5 carbon source, 2.75 g/L protein source, 9.3% inoculum ratio, 1.15 g/L. citric acid, 2.7 g/L Na2HPO4, 30 degrees C incubation temperature, 5.5 initial pH, and 9 days of incubation. This study reveals that BC production can be carried out using carob and haricot bean extracts as carbon and nitrogen sources, and CHb medium has higher buffering capacity compared to Hestrin and Schramm media. Model obtained from this study is used to predict and optimize BC production yield using CHb medium. (C) 2016 Elsevier B.V. All rights reserved