@article{MTMT:30434125, title = {Dual Action of the PN159/KLAL/MAP Peptide. Increase of Drug Penetration across Caco-2 Intestinal Barrier Model by Modulation of Tight Junctions and Plasma Membrane Permeability.}, url = {https://m2.mtmt.hu/api/publication/30434125}, author = {Bocsik, Alexandra and Gróf, Ilona and Kiss, Lóránd and Ötvös, Ferenc and Zsíros, Ottó and Daruka, Lejla and Fülöp, Lívia and Vastag, Monika and Kittel, Ágnes and Imre, Norbert and Martinek, Tamás and Pál, Csaba and Révész, Piroska and Deli, Mária Anna}, doi = {10.3390/pharmaceutics11020073}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {11}, unique-id = {30434125}, issn = {1999-4923}, abstract = {The absorption of drugs is limited by the epithelial barriers of the gastrointestinal tract. One of the strategies to improve drug delivery is the modulation of barrier function by the targeted opening of epithelial tight junctions. In our previous study the 18-mer amphiphilic PN159 peptide was found to be an effective tight junction modulator on intestinal epithelial and blood⁻brain barrier models. PN159, also known as KLAL or MAP, was described to interact with biological membranes as a cell-penetrating peptide. In the present work we demonstrated that the PN159 peptide as a penetration enhancer has a dual action on intestinal epithelial cells. The peptide safely and reversibly enhanced the permeability of Caco-2 monolayers by opening the intercellular junctions. The penetration of dextran molecules with different size and four efflux pump substrate drugs was increased several folds. We identified claudin-4 and -7 junctional proteins by docking studies as potential binding partners and targets of PN159 in the opening of the paracellular pathway. In addition to the tight junction modulator action, the peptide showed cell membrane permeabilizing and antimicrobial effects. This dual action is not general for cell-penetrating peptides (CPPs), since the other three CPPs tested did not show barrier opening effects.}, keywords = {Drug delivery; Claudin; Caco-2; Antimicrobial peptide; KLAL; PN159; absorption enhancer; cell-penetrating peptide (CPP); intestinal epithelial cells; tight junction modulator}, year = {2019}, eissn = {1999-4923}, orcid-numbers = {Fülöp, Lívia/0000-0002-8010-0129; Martinek, Tamás/0000-0003-3168-8066; Révész, Piroska/0000-0002-5336-6052; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:30679490, title = {Synthesis and Statistical Optimization of Poly (Lactic-Co-Glycolic Acid) Nanoparticles Encapsulating GLP1 Analog Designed for Oral Delivery}, url = {https://m2.mtmt.hu/api/publication/30679490}, author = {Ismail, Ruba and Sovány, Tamás and Gácsi, Attila and Ambrus, Rita and Katona, Gábor and Imre, Norbert and Pannonhalminé Csóka, Ildikó}, doi = {10.1007/s11095-019-2620-9}, journal-iso = {PHAR RES}, journal = {PHARMACEUTICAL RESEARCH}, volume = {36}, unique-id = {30679490}, issn = {0724-8741}, year = {2019}, eissn = {1573-904X}, orcid-numbers = {Ismail, Ruba/0000-0002-5122-9513; Sovány, Tamás/0000-0003-3392-7788; Katona, Gábor/0000-0003-1564-4813; Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781} } @article{MTMT:3393606, title = {Initial Risk Assessment as part of the Quality by Design in peptide drug containing formulation development}, url = {https://m2.mtmt.hu/api/publication/3393606}, author = {Pallagi, Edina and Ismail, Ruba and Paál, Tamás and Pannonhalminé Csóka, Ildikó}, doi = {10.1016/j.ejps.2018.07.003}, journal-iso = {EUR J PHARM SCI}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {122}, unique-id = {3393606}, issn = {0928-0987}, year = {2018}, eissn = {1879-0720}, pages = {160-169}, orcid-numbers = {Ismail, Ruba/0000-0002-5122-9513; Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781} } @article{MTMT:3294216, title = {Novel strategies in the oral delivery of antidiabetic peptide drugs – Insulin, GLP 1 and its analogs}, url = {https://m2.mtmt.hu/api/publication/3294216}, author = {Ismail, Ruba and Pannonhalminé Csóka, Ildikó}, doi = {10.1016/j.ejpb.2017.03.015}, journal-iso = {EUR J PHARM BIOPHARM}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS}, volume = {115}, unique-id = {3294216}, issn = {0939-6411}, year = {2017}, eissn = {1873-3441}, pages = {257-267}, orcid-numbers = {Ismail, Ruba/0000-0002-5122-9513; Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781} } @article{MTMT:3009615, title = {Reversible opening of intercellular junctions of intestinal epithelial and brain endothelial cells with tight junction modulator peptides}, url = {https://m2.mtmt.hu/api/publication/3009615}, author = {Bocsik, Alexandra and Walter, Fruzsina and Gyebrovszki, A and Fülöp, Lívia and Blasig, IE and Dabrowski, S and Ötvös, Ferenc and Tóth, András and Rákhely, Gábor and Veszelka, Szilvia and Vastag, M and Révész, Piroska and Deli, Mária Anna}, doi = {10.1016/j.xphs.2015.11.018}, journal-iso = {J PHARM SCI}, journal = {JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {105}, unique-id = {3009615}, issn = {0022-3549}, year = {2016}, eissn = {1520-6017}, pages = {754-765}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Fülöp, Lívia/0000-0002-8010-0129; Rákhely, Gábor/0000-0003-2557-3641; Révész, Piroska/0000-0002-5336-6052; 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: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:1920731, title = {Potential use of tight junction modulators to reversibly open membranous barriers and improve drug delivery}, url = {https://m2.mtmt.hu/api/publication/1920731}, author = {Deli, Mária Anna}, doi = {10.1016/j.bbamem.2008.09.016}, journal-iso = {BBA-BIOMEMBRANES}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES}, volume = {1788}, unique-id = {1920731}, issn = {0005-2736}, year = {2009}, eissn = {1879-2642}, pages = {892-910}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524} }