TY - JOUR AU - Helms, Hans C. AU - Abbott, N. Joan AU - Burek, Malgorzata AU - Cecchelli, Romeo AU - Couraud, Pierre-Olivier AU - Deli, Mária Anna AU - Förster, Carola AU - Galla, Hans J. AU - Romero, Ignacio A. AU - Shusta, Erik V. AU - Stebbins, Matthew J. AU - Vandenhaute, Elodie AU - Weksler, Babette AU - Brodin, Birger TI - In vitro models of the blood-brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use JF - JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM J2 - J CEREBR BLOOD F MET VL - 36 PY - 2016 IS - 5 SP - 862 EP - 890 PG - 29 SN - 0271-678X DO - 10.1177/0271678X16630991 UR - https://m2.mtmt.hu/api/publication/3017682 ID - 3017682 LA - English DB - MTMT ER - TY - JOUR AU - Kovacs, K AU - Jayanna, PK AU - Duke, A AU - Winner, B AU - Negrito, M AU - Angalakurthi, S AU - Yu, JC AU - Füredi, Petra AU - Ludányi, Krisztina AU - Sipos, P AU - Rockwood, GA AU - Petrikovics, I TI - A Lipid Base Formulation for Intramuscular Administration of a Novel Sulfur Donor for Cyanide Antagonism JF - CURRENT DRUG DELIVERY J2 - CURR DRUG DELIV VL - 13 PY - 2016 IS - 8 SP - 1351 EP - 1357 PG - 7 SN - 1567-2018 DO - 10.2174/1567201813666160321115851 UR - https://m2.mtmt.hu/api/publication/3078088 ID - 3078088 AB - This study represents a new formulation of the novel Cyanide (CN) antidote, Dimethyl trisulfide (DMTS), for intramuscular administration. This is a naturally occurring organosulfur molecule with the capability of reacting with CN more efficiently than the present sulfur donor type CN therapy of Thiosulfate (TS). Two types of micelles (PEG2000-DSPE and PEG2000-DSPE/TPGS) were prepared and tested for their ability to encapsulate the liquid, highly lipophilic and volatile drug, DMTS. The micellar encapsulation for DMTS does not only eliminate the possible muscle necrosis at the injection sites, but the rate of evaporation within the micelles is suppressed, that can provide a level of stability for the formulation. The method of micelle preparation was optimized and it was demonstrated that the PEG2000-DSPE preparation can dissolve up to 2.0 mg/ml of the antidote candidate. Keeping the injection volume minimized this could provide a maximum DMTS dose of 12.5 mg/kg. However, even this low dose of DMTS showed a remarkable in vivo therapeutic efficacy (2 X LD50 protection) in a mice model when injected intramuscularly. These in vitro and in vivo findings proved the efficacy of DMTS in combating CN intoxication, and the presented work gives valuable insight to micelle preparation and sets the bases for a more advanced future formulation of DMTS. LA - English DB - MTMT ER - TY - JOUR AU - Müller, Judit AU - Esso, K AU - Dargó, Gergő AU - Könczöl, Árpád AU - Balogh, György Tibor TI - Tuning the predictive capacity of the PAMPA-BBB model JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 79 PY - 2015 SP - 53 EP - 60 PG - 8 SN - 0928-0987 DO - 10.1016/j.ejps.2015.08.019 UR - https://m2.mtmt.hu/api/publication/2956822 ID - 2956822 N1 - Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budafoki út 9-11., Budapest, H-1111, Hungary Faculty of Food Science, Corvinus University of Budapest, Villányi út 29-43, Budapest, H-1118, Hungary Compound Profiling Laboratory, Gedeon Richter Plc., Gyömroi út 19-21, Budapest, H-1103, Hungary Cited By :33 Export Date: 26 February 2024 CODEN: EPSCE Correspondence Address: Balogh, G.T.; Compound Profiling Laboratory, Gedeon Richter Plc., Gyömroi út 19-21, Hungary Chemicals/CAS: acetylsalicylic acid, 493-53-8, 50-78-2, 53663-74-4, 53664-49-6, 63781-77-1; amfebutamone, 31677-93-7, 34911-55-2; amitriptyline, 50-48-6, 549-18-8; buspirone, 33386-08-2, 36505-84-7; carbamazepine, 298-46-4, 8047-84-5; cholesterol, 57-88-5; clozapine, 5786-21-0; desipramine, 50-47-5, 58-28-6; diazepam, 439-14-5; diclofenac, 15307-79-6, 15307-86-5; dimethyl sulfoxide, 67-68-5; diphenhydramine, 147-24-0, 58-73-1; fentanyl, 437-38-7; fluoxetine, 54910-89-3, 56296-78-7, 59333-67-4; hydrocortisone, 50-23-7; hydroxyzine, 2192-20-3, 64095-02-9, 68-88-2; imipramine, 113-52-0, 50-49-7; indometacin, 53-86-1, 74252-25-8, 7681-54-1; lamotrigine, 84057-84-1; maprotiline, 10262-69-8, 10347-81-6; nortriptyline, 72-69-5, 894-71-3; oxazepam, 604-75-1; phenytoin, 57-41-0, 630-93-3; progesterone, 57-83-0; promazine, 53-60-1, 58-40-2; propranolol, 13013-17-7, 318-98-9, 3506-09-0, 4199-09-1, 525-66-6; quetiapine, 111974-72-2; Membranes, Artificial Funding details: Richter Gedeon Talentum Alapítvány Funding text 1: The authors thank M. Meszlényi Sipos for the GC-FID measurements. J. Müller thanks the Gedeon Richter Talentum Foundation for the financial support. AB - Due to its robustness and versatility, several variations of the blood-brain barrier specific parallel artificial membrane permeability assay (PAMPA-BBB) have been reported in the central nervous system (CNS) drug discovery practice. In this study, the impact of the main assay parameters on the predictive power of PAMPA-BBB was thoroughly investigated with 27, passively BBB-transported drug molecules with in vivo logBB data. The single and combined effects of the following variables were systematically studied and optimized: incubation time and temperature (4 vs. 18 h, RT vs. 37°C), type of the read-out (UV-reader vs. HPLC), solvent composition (n-dodecane/n-hexane), lipid concentration (0-10 w/v % PBLE), cholesterol content (0-1.66 w/v %), and thickness of the lipid membrane, and the DMSO cosolvent content (5-20 v/v %), respectively. Based on our results, solvent-driven and lipid-driven mechanisms of diffusion were identified in different assay conditions. Moreover, the analysis of membrane retention (MR%; the mole fraction of solute "lost" to the membrane) data obtained at various membrane compositions (volume of solvent and concentration of phospholipids) revealed the compound-specific nature of this parameter. The optimized conditions for the PAMPA-BBB were the following: 4 h incubation at 37°C, detection by HPLC-DAD, iso-pH conditions (pH = 7.4) with 5 v/v % DMSO content in buffer solutions, and PBLE (10 w/v %; without cholesterol) as membrane dissolved in the mixture of n-hexane:n-dodecane 3:1. © 2015 Elsevier B.V.All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Walter, Fruzsina AU - Veszelka, Szilvia AU - Pásztói, Mária AU - Péterfi, Zoltán Attila AU - Tóth, András AU - Rákhely, Gábor AU - Cervenak, László AU - Ábrahám, CS AU - Deli, Mária Anna TI - Tesmilifene modifies brain endothelial functions and opens the blood-brain/blood-glioma barrier JF - JOURNAL OF NEUROCHEMISTRY J2 - J NEUROCHEM VL - 134 PY - 2015 IS - 6 SP - 1040 EP - 1054 PG - 15 SN - 0022-3042 DO - 10.1111/jnc.13207 UR - https://m2.mtmt.hu/api/publication/2912411 ID - 2912411 LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Lóránd AU - Virághné Hellinger, Éva AU - Pilbat, Ana Maria AU - Kittel, Ágnes AU - Török, Zsolt AU - Füredi, András AU - Szakács, Gergely AU - Veszelka, Szilvia AU - Sipos, Péter AU - Ózsvári, B AU - Puskás, László AU - Vastag, M AU - Révész, Piroska AU - Deli, Mária Anna TI - Sucrose esters increase drug penetration, but do not inhibit P-glycoprotein in Caco-2 intestinal epithelial cells JF - JOURNAL OF PHARMACEUTICAL SCIENCES J2 - J PHARM SCI VL - 103 PY - 2014 IS - 10 SP - 3107 EP - 3119 PG - 13 SN - 0022-3549 DO - 10.1002/jps.24085 UR - https://m2.mtmt.hu/api/publication/2709800 ID - 2709800 AB - Sucrose fatty acid esters are increasingly used as excipients in pharmaceutical products, but few data are available on their toxicity profile, mode of action, and efficacy on intestinal epithelial models. Three water-soluble sucrose esters, palmitate (P-1695), myristate (M-1695), laurate (D-1216), and two reference absorption enhancers, Tween 80 and Cremophor RH40, were tested on Caco-2 cells. Caco-2 monolayers formed a good barrier as reflected by high transepithelial resistance and positive immunostaining for junctional proteins claudin-1, ZO-1, and -catenin. Sucrose esters in nontoxic concentrations significantly reduced resistance and impedance, and increased permeability for atenolol, fluorescein, vinblastine, and rhodamine 123 in Caco-2 monolayers. No visible opening of the tight junctions was induced by sucrose esters assessed by immunohistochemistry and electron microscopy, but some alterations were seen in the structure of filamentous actin microfilaments. Sucrose esters fluidized the plasma membrane and enhanced the accumulation of efflux transporter ligands rhodamine 123 and calcein AM in epithelial cells, but did not inhibit the P-glycoprotein (P- gp)-mediated calcein AM accumulation in MES-SA/Dx5 cell line. These data indicate that in addition to their dissolution-increasing properties sucrose esters can enhance drug permeability through both the transcellular and paracellular routes without inhibiting P- LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Lóránd AU - Walter, Fruzsina AU - Bocsik, Alexandra AU - Veszelka, Szilvia AU - Ózsvári, B AU - Puskás, László AU - Révész, Piroska AU - Deli, Mária Anna TI - Kinetic Analysis of the Toxicity of Pharmaceutical Excipients Cremophor EL and RH40 on Endothelial and Epithelial Cells JF - JOURNAL OF PHARMACEUTICAL SCIENCES J2 - J PHARM SCI VL - 102 PY - 2013 IS - 4 SP - 1173 EP - 1181 PG - 9 SN - 0022-3549 DO - 10.1002/jps.23458 UR - https://m2.mtmt.hu/api/publication/2153338 ID - 2153338 N1 - Cited By :78 Export Date: 20 June 2022 CODEN: JPMSA LA - English DB - MTMT ER - TY - JOUR AU - Veszelka, Szilvia AU - Tóth, Andrea AU - Walter, Fruzsina AU - Datki, Zsolt László AU - Jánosi-Mózes, Emese AU - Fülöp, Lívia AU - Bozsó, Zsolt AU - Virághné Hellinger, Éva AU - Vastag, M AU - Orsolits, Barbara AU - Környei, Zsuzsanna AU - Penke, Botond AU - Deli, Mária Anna TI - Docosahexaenoic acid reduces amyloid β-induced toxicity in cells of the neurovascular unit JF - JOURNAL OF ALZHEIMER'S DISEASE J2 - J ALZHEIMERS DIS VL - 36 PY - 2013 IS - 3 SP - 487 EP - 501 PG - 15 SN - 1387-2877 DO - 10.3233/JAD-120163 UR - https://m2.mtmt.hu/api/publication/2246475 ID - 2246475 LA - English DB - MTMT ER - TY - JOUR AU - Virághné Hellinger, Éva AU - Veszelka, Szilvia AU - Tóth, Andrea AU - Walter, Fruzsina AU - Kittel, Ágnes AU - Bakk, ML AU - Tihanyi, Károly AU - Háda, Viktor AU - Nakagawa, S AU - Thuy, DH AU - Niwa, M AU - Deli, Mária Anna AU - Vastag, M TI - Comparison of brain capillary endothelial cell based and epithelial cell based (MDCK-MDR1, Caco-2, and VB-Caco-2) surrogate blood-brain barrier penetration models JF - EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS J2 - EUR J PHARM BIOPHARM VL - 82 PY - 2012 IS - 2 SP - 340 EP - 351 PG - 12 SN - 0939-6411 DO - 10.1016/j.ejpb.2012.07.020 UR - https://m2.mtmt.hu/api/publication/2034983 ID - 2034983 N1 - Division of Pharmacology and Drug Safety Research, Gedeon Richter Plc., Gyömri út. 19-21, H-1103 Budapest, Hungary Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Spectroscopic Research, Gedeon Richter Plc., Budapest, Hungary Department of Pharmacology 1, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki, Japan BBB Laboratory, PharmaCo-Cell Co. Ltd., Nagasaki, Japan Cited By :108 Export Date: 1 June 2020 CODEN: EJPBE Correspondence Address: Vastag, M.; Division of Pharmacology and Drug Safety Research, Gedeon Richter Plc., Gyömri út. 19-21, H-1103 Budapest, Hungary; email: m.vastag@richter.hu Chemicals/CAS: aldosterone, 52-39-1, 6251-69-0; atenolol, 29122-68-7, 93379-54-5; caffeine, 58-08-2; chlorothiazide, 58-94-6, 7085-44-1; cimetidine, 51481-61-9, 70059-30-2; colchicine, 64-86-8; corticosterone, 50-22-6; dexamethasone, 50-02-2; digoxin, 20830-75-5, 57285-89-9; estradiol, 50-28-2; furosemide, 54-31-9; hydrocortisone, 50-23-7; indometacin, 53-86-1, 74252-25-8, 7681-54-1; ketoconazole, 65277-42-1; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; loperamide, 34552-83-5, 53179-11-6; metoprolol, 37350-58-6; multidrug resistance protein, 149200-37-3, 208997-77-7; omeprazole, 73590-58-6, 95510-70-6; paracetamol, 103-90-2; phenazone, 60-80-0; phenytoin, 57-41-0, 630-93-3; progesterone, 57-83-0; propranolol, 13013-17-7, 318-98-9, 3506-09-0, 4199-09-1, 525-66-6; quinidine, 56-54-2; ranitidine, 66357-35-5, 66357-59-3; salicylic acid, 63-36-5, 69-72-7; theobromine, 83-67-0; verapamil, 152-11-4, 52-53-9; vinblastine, 865-21-4; P-Glycoprotein LA - English DB - MTMT ER - TY - JOUR AU - Kürti, Levente AU - Veszelka, Szilvia AU - Bocsik, Alexandra AU - Dung, Ngo Thi Khue AU - Ozsvari, B AU - Puskás, László AU - Kittel, Ágnes AU - Révész, Piroska AU - Deli, Mária Anna TI - The effect of sucrose esters on a culture model of the nasal barrier JF - TOXICOLOGY IN VITRO J2 - TOXICOL IN VITRO VL - 26 PY - 2012 IS - 3 SP - 445 EP - 454 PG - 10 SN - 0887-2333 DO - 10.1016/j.tiv.2012.01.015 UR - https://m2.mtmt.hu/api/publication/1847178 ID - 1847178 N1 - Funding Agency and Grant Number: European UnionEuropean Union (EU) [TAMOP-4.2.1/B-09/1/KONV-2010-0005]; European Regional Development FundEuropean Union (EU) Funding text: The Project named "TAMOP-4.2.1/B-09/1/KONV-2010-0005 - Creating the Centre of Excellence at the University of Szeged" is supported by the European Union and co-financed by the European Regional Development Fund. Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári Krt. 62, H-6726 Szeged, Hungary Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary Avidin Ltd., Közép fasor 52, H-6726 Szeged, Hungary Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, H-1083 Budapest, Hungary Cited By :39 Export Date: 9 October 2020 CODEN: TIVIE Correspondence Address: Deli, M.A.; Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári Krt. 62, H-6726 Szeged, Hungary; email: deli@brc.hu Chemicals/CAS: cremophor, 39279-69-1, 51142-51-9; polysorbate 80, 8050-83-7, 9005-65-6; sucrose laurate, 25339-99-5; Dextrans, 9004-54-0; Excipients; Fluorescein-5-isothiocyanate, 3326-32-7; L-Lactate Dehydrogenase, 1.1.1.27; Polyethylene Glycols; Polysorbates; Sucrose, 57-50-1; cremophor, 39279-69-1; fluorescein isothiocyanate dextran; sucrose monolaurate, 25339-99-5; sucrose myristate, 9042-71-1 Funding details: European Commission, EC Funding details: European Regional Development Fund, FEDER Funding text 1: The Project named “TÁMOP-4.2.1/B-09/1/KONV-2010-0005 – Creating the Centre of Excellence at the University of Szeged” is supported by the European Union and co-financed by the European Regional Development Fund. AB - Sucrose esters are effective solubilizers and there is an interest to use them as pharmaceutical excipients for nasal dru1 delivery. We have determined for the first time the non-toxic doses of laurate and myristate sucrose esters by four independent methods, and their effects on epithelial permeability using RPMI 2650 human nasal epithelial cell line. Based on real-time cell electronic sensing, MTT dye conversion and lactate dehydrogenase release methods reference surfactant Cremophor RH40 proved to be the least toxic excipient, and could be used at 5mg/mL concentration for 1h in epithelial cells without cellular damage. The non-toxic dose of Tween 80 was 1mg/mL, while the dose of laurate and myristate sucrose esters that could be safely used on cells for 1h was 0.1mg/mL. Both the reference surfactants and the sucrose esters significantly enhanced the permeability of epithelial cell layers for the paracellular marker FITC-labelled 4.4kDa dextran at 0.1mg/mL concentration. The effects of sucrose esters on epithelial permeability were dose-dependent. These data indicate that laurate and myristate sucrose esters can be potentially used as permeability enhancers in nasal formulations to augment drug delivery to the systemic circulation. LA - English DB - MTMT ER - TY - JOUR AU - Nakagawa, S AU - Deli, Mária Anna AU - Kawaguchi, H AU - Shimizudani, T AU - Shimono, T AU - Kittel, Ágnes AU - Tanaka, K AU - Niwa, M TI - A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes JF - NEUROCHEMISTRY INTERNATIONAL J2 - NEUROCHEM INT VL - 54 PY - 2009 IS - 3-4 SP - 253 EP - 263 PG - 11 SN - 0197-0186 DO - 10.1016/j.neuint.2008.12.002 UR - https://m2.mtmt.hu/api/publication/109905 ID - 109905 AB - Blood-brain barrier (BBB) characteristics are induced and maintained by cross-talk between brain microvessel endothelial cells and neighbouring elements of the neurovascular unit. While pericytes are the cells situated closest to brain endothelial cells morphologically and share a common basement membrane, they have not been used in co-culture BBB models for testing drug permeability. We have developed and characterized a new syngeneic BBB model using primary cultures of the three main cell types of cerebral microvessels. The co-culture of endothelial cells, pericytes and astrocytes mimick the anatomical situation in vivo. In the presence of both pericytes and astrocytes rat brain endothelial cells expressed enhanced levels of tight junction (TJ) proteins occludin, claudin-5 and ZO-1 with a typical localization at the cell borders. Further morphological evidence of the presence of interendothelial TJs was provided by electron microscopy. The transendothelial electrical resistance (TEER) of brain endothelial monolayers in triple co-culture, indicating the tightness of TJs reached 400Omegacm(2) on average, while the endothelial permeability coefficients (P(e)) for fluorescein was in the range of 3x10(-6)cm/s. Brain endothelial cells in the new model expressed glucose transporter-1, efflux transporters P-glycoprotein and multidrug resistance protein-1, and showed a polarized transport of rhodamine 123, a ligand for P-glycoprotein. To further characterize the model, drug permeability assays were performed using a set of 19 compounds with known in vivo BBB permeability. Good correlation (R(2)=0.89) was found between in vitroP(e) values obtained from measurements on the BBB model and in vivo BBB permeability data. The new BBB model, which is the first model to incorporate pericytes in a triple co-culture setting, can be a useful tool for research on BBB physiology and pathology and to test candidate compounds for centrally acting drugs. LA - English DB - MTMT ER - TY - JOUR AU - Deli, Mária Anna AU - Abraham, Csongor S. AU - Kataoka, Yasufumi AU - Niwa, Masami TI - Permeability studies on in vitro blood-brain barrier models: Physiology, pathology, and pharmacology JF - CELLULAR AND MOLECULAR NEUROBIOLOGY J2 - CELL MOL NEUROBIOL VL - 25 PY - 2005 IS - 1 SP - 59 EP - 127 PG - 69 SN - 0272-4340 DO - 10.1007/s10571-004-1377-8 UR - https://m2.mtmt.hu/api/publication/1913801 ID - 1913801 LA - English DB - MTMT ER -