Bocsik, Alexandra and Gróf, Ilona and Kiss, Lóránd and Ötvös, Ferenc and Zsíros, Ottó and Daruka, Lejla and Kittel, Ágnes and Imre, Norbert and Pál, Csaba and Deli, Mária Anna (2019) Dual Action of the PN159/KLAL/MAP Peptide. Pharmaceutics, 11 (2). ISSN 1999-4923
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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.
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| Additional Information: | Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [GINOP-2.2.1-15-2016-00007] Funding text: This research was funded by the National Research, Development and Innovation Office of Hungary, grant number GINOP-2.2.1-15-2016-00007. Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, H-6726, Hungary Department of Pathophysiology, University of Szeged, Szeged, H-6701, Hungary Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, H-6726, Hungary Plant Biology, Biological Research Centre, Hungarian Academy of Sciences, Szeged, H-6726, Hungary Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary Doctoral School in Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Department of Medical Chemistry, University of Szeged, Szeged, H-6720, Hungary Division of Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, H-1103, Hungary Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, H-1450, Hungary Department of Pharmaceutical Technology, University of Szeged, Szeged, H-6720, Hungary Cited By :2 Export Date: 27 August 2019 Correspondence Address: Deli, M.A.; Institute of Biophysics, Biological Research Centre, Hungarian Academy of SciencesHungary; email: deli.maria@brc.mta.hu Chemicals/CAS: atenolol, 29122-68-7, 93379-54-5; cimetidine, 51481-61-9, 70059-30-2; dextran, 87915-38-6, 9014-78-2; quinidine, 56-54-2; verapamil, 152-11-4, 52-53-9 Tradenames: pn 159 |
| Uncontrolled Keywords: | Drug delivery; Claudin; Caco-2; Antimicrobial peptide; KLAL; PN159; absorption enhancer; cell-penetrating peptide (CPP); intestinal epithelial cells; tight junction modulator; |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3020 Biophysics / biofizika R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 21 Nov 2019 12:47 |
| Last Modified: | 21 Nov 2019 12:47 |
| URI: | http://real.mtak.hu/id/eprint/103499 |
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