@article{MTMT:3017682, title = {In vitro models of the blood-brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use}, url = {https://m2.mtmt.hu/api/publication/3017682}, author = {Helms, Hans C. and Abbott, N. Joan and Burek, Malgorzata and Cecchelli, Romeo and Couraud, Pierre-Olivier and Deli, Mária Anna and Förster, Carola and Galla, Hans J. and Romero, Ignacio A. and Shusta, Erik V. and Stebbins, Matthew J. and Vandenhaute, Elodie and Weksler, Babette and Brodin, Birger}, doi = {10.1177/0271678X16630991}, journal-iso = {J CEREBR BLOOD F MET}, journal = {JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM}, volume = {36}, unique-id = {3017682}, issn = {0271-678X}, year = {2016}, eissn = {1559-7016}, pages = {862-890}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:3078088, title = {A Lipid Base Formulation for Intramuscular Administration of a Novel Sulfur Donor for Cyanide Antagonism}, url = {https://m2.mtmt.hu/api/publication/3078088}, author = {Kovacs, K and Jayanna, PK and Duke, A and Winner, B and Negrito, M and Angalakurthi, S and Yu, JC and Füredi, Petra and Ludányi, Krisztina and Sipos, P and Rockwood, GA and Petrikovics, I}, doi = {10.2174/1567201813666160321115851}, journal-iso = {CURR DRUG DELIV}, journal = {CURRENT DRUG DELIVERY}, volume = {13}, unique-id = {3078088}, issn = {1567-2018}, abstract = {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.}, year = {2016}, eissn = {1875-5704}, pages = {1351-1357}, orcid-numbers = {Füredi, Petra/0000-0003-3618-8968; Ludányi, Krisztina/0000-0002-2380-9529} } @article{MTMT:2956822, title = {Tuning the predictive capacity of the PAMPA-BBB model}, url = {https://m2.mtmt.hu/api/publication/2956822}, author = {Müller, Judit and Esso, K and Dargó, Gergő and Könczöl, Árpád and Balogh, György Tibor}, doi = {10.1016/j.ejps.2015.08.019}, journal-iso = {EUR J PHARM SCI}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {79}, unique-id = {2956822}, issn = {0928-0987}, abstract = {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.}, keywords = {LIPOPHILICITY; ASSAY; CLOZAPINE; ARTICLE; PREDICTION; Incubation temperature; high performance liquid chromatography; Molecular weight; priority journal; phenytoin; lamotrigine; carbamazepine; DIAZEPAM; DIFFUSION; Dimethyl Sulfoxide; Permeability; Blood-Brain Barrier; PROGESTERONE; cholesterol; hydrocortisone; ultraviolet radiation; membrane lipid; lipid membrane; indometacin; solvent; lipid composition; unindexed drug; diphenhydramine; physical chemistry; acetylsalicylic acid; diclofenac; fluoxetine; PROPRANOLOL; oxazepam; quetiapine; fentanyl; blood brain barrier; imipramine; amitriptyline; drug penetration; incubation time; buspirone; desipramine; membrane permeability; radiation absorption; amfebutamone; nortriptyline; maprotiline; PAMPA; hydroxyzine; promazine; microplate reader; blood brain barrier specific parallel artificial membrane permeability assay; apparent permeability; Cosolvent}, year = {2015}, eissn = {1879-0720}, pages = {53-60}, orcid-numbers = {Dargó, Gergő/0000-0002-1141-8379; Balogh, György Tibor/0000-0003-3347-1880} } @article{MTMT:2912411, title = {Tesmilifene modifies brain endothelial functions and opens the blood-brain/blood-glioma barrier}, url = {https://m2.mtmt.hu/api/publication/2912411}, author = {Walter, Fruzsina and Veszelka, Szilvia and Pásztói, Mária and Péterfi, Zoltán Attila and Tóth, András and Rákhely, Gábor and Cervenak, László and Ábrahám, CS and Deli, Mária Anna}, doi = {10.1111/jnc.13207}, journal-iso = {J NEUROCHEM}, journal = {JOURNAL OF NEUROCHEMISTRY}, volume = {134}, unique-id = {2912411}, issn = {0022-3042}, year = {2015}, eissn = {1471-4159}, pages = {1040-1054}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Rákhely, Gábor/0000-0003-2557-3641; Cervenak, László/0000-0003-0166-8697; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:2709800, title = {Sucrose esters increase drug penetration, but do not inhibit P-glycoprotein in Caco-2 intestinal epithelial cells}, url = {https://m2.mtmt.hu/api/publication/2709800}, author = {Kiss, Lóránd and Virághné Hellinger, Éva and Pilbat, Ana Maria and Kittel, Ágnes and Török, Zsolt and Füredi, András and Szakács, Gergely and Veszelka, Szilvia and Sipos, Péter and Ózsvári, B and Puskás, László and Vastag, M and Révész, Piroska and Deli, Mária Anna}, doi = {10.1002/jps.24085}, journal-iso = {J PHARM SCI}, journal = {JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {103}, unique-id = {2709800}, issn = {0022-3549}, abstract = {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-}, year = {2014}, eissn = {1520-6017}, pages = {3107-3119}, orcid-numbers = {Füredi, András/0000-0002-7883-9901; Révész, Piroska/0000-0002-5336-6052; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:2153338, title = {Kinetic Analysis of the Toxicity of Pharmaceutical Excipients Cremophor EL and RH40 on Endothelial and Epithelial Cells}, url = {https://m2.mtmt.hu/api/publication/2153338}, author = {Kiss, Lóránd and Walter, Fruzsina and Bocsik, Alexandra and Veszelka, Szilvia and Ózsvári, B and Puskás, László and Révész, Piroska and Deli, Mária Anna}, doi = {10.1002/jps.23458}, journal-iso = {J PHARM SCI}, journal = {JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {102}, unique-id = {2153338}, issn = {0022-3549}, year = {2013}, eissn = {1520-6017}, pages = {1173-1181}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Révész, Piroska/0000-0002-5336-6052; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:2246475, title = {Docosahexaenoic acid reduces amyloid β-induced toxicity in cells of the neurovascular unit}, url = {https://m2.mtmt.hu/api/publication/2246475}, author = {Veszelka, Szilvia and Tóth, Andrea and Walter, Fruzsina and Datki, Zsolt László and Jánosi-Mózes, Emese and Fülöp, Lívia and Bozsó, Zsolt and Virághné Hellinger, Éva and Vastag, M and Orsolits, Barbara and Környei, Zsuzsanna and Penke, Botond and Deli, Mária Anna}, doi = {10.3233/JAD-120163}, journal-iso = {J ALZHEIMERS DIS}, journal = {JOURNAL OF ALZHEIMER'S DISEASE}, volume = {36}, unique-id = {2246475}, issn = {1387-2877}, year = {2013}, eissn = {1875-8908}, pages = {487-501}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Datki, Zsolt László/0000-0002-2537-4741; Jánosi-Mózes, Emese/0000-0003-1532-289X; Fülöp, Lívia/0000-0002-8010-0129; Bozsó, Zsolt/0000-0002-5713-3096; Penke, Botond/0000-0003-0938-0567; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:2034983, title = {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}, url = {https://m2.mtmt.hu/api/publication/2034983}, author = {Virághné Hellinger, Éva and Veszelka, Szilvia and Tóth, Andrea and Walter, Fruzsina and Kittel, Ágnes and Bakk, ML and Tihanyi, Károly and Háda, Viktor and Nakagawa, S and Thuy, DH and Niwa, M and Deli, Mária Anna and Vastag, M}, doi = {10.1016/j.ejpb.2012.07.020}, journal-iso = {EUR J PHARM BIOPHARM}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS}, volume = {82}, unique-id = {2034983}, issn = {0939-6411}, year = {2012}, eissn = {1873-3441}, pages = {340-351}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:1847178, title = {The effect of sucrose esters on a culture model of the nasal barrier}, url = {https://m2.mtmt.hu/api/publication/1847178}, author = {Kürti, Levente and Veszelka, Szilvia and Bocsik, Alexandra and Dung, Ngo Thi Khue and Ozsvari, B and Puskás, László and Kittel, Ágnes and Révész, Piroska and Deli, Mária Anna}, doi = {10.1016/j.tiv.2012.01.015}, journal-iso = {TOXICOL IN VITRO}, journal = {TOXICOLOGY IN VITRO}, volume = {26}, unique-id = {1847178}, issn = {0887-2333}, abstract = {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.}, year = {2012}, eissn = {1879-3177}, pages = {445-454}, orcid-numbers = {Révész, Piroska/0000-0002-5336-6052; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:109905, title = {A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes}, url = {https://m2.mtmt.hu/api/publication/109905}, author = {Nakagawa, S and Deli, Mária Anna and Kawaguchi, H and Shimizudani, T and Shimono, T and Kittel, Ágnes and Tanaka, K and Niwa, M}, doi = {10.1016/j.neuint.2008.12.002}, journal-iso = {NEUROCHEM INT}, journal = {NEUROCHEMISTRY INTERNATIONAL}, volume = {54}, unique-id = {109905}, issn = {0197-0186}, abstract = {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.}, year = {2009}, eissn = {1872-9754}, pages = {253-263}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:1913801, title = {Permeability studies on in vitro blood-brain barrier models: Physiology, pathology, and pharmacology}, url = {https://m2.mtmt.hu/api/publication/1913801}, author = {Deli, Mária Anna and Abraham, Csongor S. and Kataoka, Yasufumi and Niwa, Masami}, doi = {10.1007/s10571-004-1377-8}, journal-iso = {CELL MOL NEUROBIOL}, journal = {CELLULAR AND MOLECULAR NEUROBIOLOGY}, volume = {25}, unique-id = {1913801}, issn = {0272-4340}, year = {2005}, eissn = {1573-6830}, pages = {59-127}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524} }