TY - JOUR AU - Lázár, Viktória AU - Martins, Ana AU - Spohn, Réka AU - Daruka, Lejla AU - Grézal, Gábor AU - Fekete, Gergely AU - Számel, Mónika AU - Jangir, Pramod Kumar AU - Kintses, Bálint AU - Csörgő, Bálint AU - Nyerges, Ákos AU - Györkei, Ádám AU - Kincses, András AU - Dér, András AU - Walter, Fruzsina AU - Deli, Mária Anna AU - Zsoldiné Urbán, Edit AU - Hegedüs, Zsófia AU - Olajos, Gábor AU - Méhi, Orsolya Katinka AU - Bálint, Balázs AU - Nagy, István AU - Martinek, Tamás AU - Papp, Balázs AU - Pál, Csaba TI - Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides JF - NATURE MICROBIOLOGY J2 - NAT MICROBIOL VL - 3 PY - 2018 IS - 6 SP - 718 EP - 731 PG - 14 SN - 2058-5276 DO - 10.1038/s41564-018-0164-0 UR - https://m2.mtmt.hu/api/publication/3378998 ID - 3378998 N1 - Megosztott első szerzőség. These authors contributed equally to this work: Viktória Lázár and Ana Martins. AB - Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic-resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug-resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-administered as an adjuvant, the antimicrobial peptide glycine-leucine-amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic-resistant infections. LA - English DB - MTMT ER - TY - JOUR AU - Veszelka, Szilvia AU - Tóth, András AU - Walter, Fruzsina AU - Tóth, Andrea AU - Gróf, Ilona AU - Mészáros, Mária AU - Bocsik, Alexandra AU - Virághné Hellinger, Éva AU - Vastag, M AU - Rákhely, Gábor AU - Deli, Mária Anna TI - Comparison of a rat primary cell-based blood-brain barrier model with epithelial and brain endothelial cell lines: gene expression and drug transport JF - FRONTIERS IN MOLECULAR NEUROSCIENCE J2 - FRONT MOL NEUROSCI VL - 11 ET - 0 PY - 2018 PG - 20 SN - 1662-5099 DO - 10.3389/fnmol.2018.00166 UR - https://m2.mtmt.hu/api/publication/3365532 ID - 3365532 N1 - These authors have contributed equally to this work: Szilvia Veszelka, András Tóth. AB - Cell culture-based blood-brain barrier (BBB) models are useful tools for screening of CNS drug candidates. Cell sources for BBB models include primary brain endothelial cells or immortalized brain endothelial cell lines. Despite their well-known differences, epithelial cell lines are also used as surrogate models for testing neuropharmaceuticals. The aim of the present study was to compare the expression of selected BBB related genes including tight junction proteins, solute carriers (SLC), ABC transporters, metabolic enzymes and to describe the paracellular properties of nine different culture models. To establish a primary BBB model rat brain capillary endothelial cells were co-cultured with rat pericytes and astrocytes (EPA). As other BBB and surrogate models four brain endothelial cells lines, rat GP8 and RBE4 cells, and human hCMEC/D3 cells with or without lithium treatment (D3 and D3L), and four epithelial cell lines, native human intestinal Caco-2 and high P-glycoprotein expressing vinblastine-selected VB-Caco-2 cells, native MDCK and MDR1 transfected MDCK canine kidney cells were used. To test transporter functionality, the permeability of 12 molecules, glucopyranose, valproate, baclofen, gabapentin, probenecid, salicylate, rosuvastatin, pravastatin, atorvastatin, tacrine, donepezil, was also measured in the EPA and epithelial models. Among the junctional protein genes, the expression level of occludin was high in all models except the GP8 and RBE4 cells, and each model expressed a unique claudin pattern. Major BBB efflux (P-glycoprotein or ABCB1) and influx transporters (GLUT-1, LAT-1) were present in all models at mRNA levels. The transcript of BCRP (ABCG2) was not expressed in MDCK, GP8 and RBE4 cells. The absence of gene expression of important BBB efflux and influx transporters BCRP, MRP6,-9, MCT6,-8, PHT2, OATPs in one or both types of epithelial models suggests that Caco-2 or MDCK models are not suitable to test drug candidates which are substrates of these transporters. Brain endothelial cell lines GP8, RBE4, D3 and D3L did not form a restrictive paracellular barrier necessary for screening small molecular weight pharmacons. Therefore, among the tested culture models, the primary cell-based EPA model is suitable for the functional analysis of the BBB. © 2018 Veszelka, Tóth, Walter, Tóth, Gróf, Mészáros, Bocsik, Hellinger, Vastag, Rákhely and Deli. LA - English DB - MTMT ER - TY - JOUR AU - Dithmer, S AU - Staat, C AU - Müller, C AU - Ku, M-C AU - Pohlmann, A AU - Niendorf, T AU - Gehne, N AU - Fallier-Becker, P AU - Kittel, Ágnes AU - Walter, Fruzsina AU - Veszelka, Szilvia AU - Deli, Mária Anna AU - Blasig, R AU - Haseloff, RF AU - Blasig, IE AU - Winkler, L TI - Claudin peptidomimetics modulate tissue barriers for enhanced drug delivery JF - ANNALS OF THE NEW YORK ACADEMY OF SCIENCES J2 - ANN NY ACAD SCI VL - 1397 PY - 2017 IS - 1 SP - 169 EP - 184 PG - 16 SN - 0077-8923 DO - 10.1111/nyas.13359 UR - https://m2.mtmt.hu/api/publication/3242472 ID - 3242472 LA - English DB - MTMT ER - TY - JOUR AU - Bocsik, Alexandra AU - Walter, Fruzsina AU - Gyebrovszki, A AU - Fülöp, Lívia AU - Blasig, IE AU - Dabrowski, S AU - Ötvös, Ferenc AU - Tóth, András AU - Rákhely, Gábor AU - Veszelka, Szilvia AU - Vastag, M AU - Révész, Piroska AU - Deli, Mária Anna TI - Reversible opening of intercellular junctions of intestinal epithelial and brain endothelial cells with tight junction modulator peptides JF - JOURNAL OF PHARMACEUTICAL SCIENCES J2 - J PHARM SCI VL - 105 PY - 2016 IS - 2 SP - 754 EP - 765 PG - 12 SN - 0022-3549 DO - 10.1016/j.xphs.2015.11.018 UR - https://m2.mtmt.hu/api/publication/3009615 ID - 3009615 LA - English DB - MTMT ER - TY - JOUR AU - Róka, Eszter AU - Vecsernyés, Miklós AU - Bácskay, Ildikó AU - Félix, C AU - Rhimi, M AU - Coleman, AW AU - Perret, F TI - para-sulphonato-calix[n]arenes as selective activators for the passage of molecules across the Caco-2 model intestinal membrane JF - CHEMICAL COMMUNICATIONS J2 - CHEM COMMUN VL - 51 PY - 2015 IS - 45 SP - 9374 EP - 9376 PG - 3 SN - 1359-7345 DO - 10.1039/c5cc01777g UR - https://m2.mtmt.hu/api/publication/2932595 ID - 2932595 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 - 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 - Virághné Hellinger, Éva AU - Bakk, ML AU - Pócza, Péter AU - Tihanyi, Károly AU - Vastag, M TI - Drug penetration model of vinblastine-treated Caco-2 cultures JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 41 PY - 2010 IS - 1 SP - 96 EP - 106 PG - 11 SN - 0928-0987 DO - 10.1016/j.ejps.2010.05.015 UR - https://m2.mtmt.hu/api/publication/1753490 ID - 1753490 N1 - WoS:hiba:000280875700012 2019-03-04 01:46 cikkazonosító nem egyezik LA - English DB - MTMT ER - TY - JOUR AU - Deli, Mária Anna TI - Potential use of tight junction modulators to reversibly open membranous barriers and improve drug delivery JF - BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES J2 - BBA-BIOMEMBRANES VL - 1788 PY - 2009 IS - 4 SP - 892 EP - 910 PG - 19 SN - 0005-2736 DO - 10.1016/j.bbamem.2008.09.016 UR - https://m2.mtmt.hu/api/publication/1920731 ID - 1920731 N1 - Megjegyzés-20963954 FU: National Office for Research and Technology [RET 08/2004]; Hungarian : Ministry of Health [ETT 589/2006] FX: This work was supported by grants from the National Office for Research : and Technology (RET 08/2004) and the Hungarian Ministry of Health ETT : 589/2006. The help of Dr. Csongor AbrahAm for critical reading of the : manuscript is gratefully acknowledged. Megjegyzés-21456976 DI: 10.1016/j.bbamem.2008.09.016 Megjegyzés-22110013 DI: 10.1016/j.bbamem.2008.09.016 Megjegyzés-22120929 DI: 10.1016/j.bbamem.2008.09.016 Megjegyzés-22171311 DI: 10.1016/j.bbamem.2008.09.016 Megjegyzés-22182274 DI: 10.1016/j.bbamem.2008.09.016 Megjegyzés-22191831 DI: 10.1016/j.bbamem.2008.09.016 Megjegyzés-22193458 DI: 10.1016/j.bbamem.2008.09.016 Megjegyzés-22195546 DI: 10.1016/j.bbamem.2008.09.016 Megjegyzés-22217622 DI: 10.1016/j.bbamem.2008.09.016 Megjegyzés-20963631 FU: National Office for Research and Technology [RET 08/2004]; Hungarian : Ministry of Health [ETT 589/2006] FX: This work was supported by grants from the National Office for Research : and Technology (RET 08/2004) and the Hungarian Ministry of Health ETT : 589/2006. The help of Dr. Csongor AbrahAm for critical reading of the : manuscript is gratefully acknowledged. Megjegyzés-21461393 Chemicals/CAS: calnexin, 139873-08-8; cyclodextrin, 12619-70-4; occludin, 176304-61-3; uvomorulin, 112956-45-3; Chelating Agents; Cholera Toxin, 9012-63-9; Membrane Proteins; claudin 1; occludin; zonulin LA - English DB - MTMT ER -