Evidence map›Paper›PMID 30744154›Full record

ArticlePharmaceutics2019

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.

Alexandra Bocsik, Ilona Gróf, Lóránd Kiss, Ferenc Ötvös, Ottó Zsíros, Lejla Daruka, Lívia Fülöp, Monika Vastag, Ágnes Kittel, Norbert Imre and 4 more

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
5.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 56 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Gastrointestinal Permeation Enhancers Beyond Sodium Caprate and SNAC - What is Coming Next?Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  6. Review
  7. Article
  8. Review
  9. A Second Life for MAP, a Model Amphipathic Peptide.International journal of molecular sciences · 2022
    Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Alexandra BocsikInstitute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, H-6726, Szeged, Hungary. bocsik.alexandra@brc.mta.hu.
Ilona GrófInstitute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, H-6726, Szeged, Hungary. ilona.grof@brc.mta.hu.
Lóránd KissInstitute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, H-6726, Szeged, Hungary. kiss.lorand@med.u-szeged.hu.
Ferenc ÖtvösInstitute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, H-6726, Szeged, Hungary. otvos.ferenc@brc.mta.hu.
Ottó ZsírosPlant Biology, Biological Research Centre, Hungarian Academy of Sciences, H-6726, Szeged, Hungary. zsiros.otto@brc.mta.hu.
Lejla DarukaSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary. daruka.lejla@brc.mta.hu.
Lívia FülöpDepartment of Medical Chemistry, University of Szeged, H-6720 Szeged, Hungary. fulop.livia@med.u-szeged.hu.
Monika VastagDivision of Pharmacology and Drug Safety Research, Gedeon Richter Plc., H-1103 Budapest, Hungary. m.vastag@richter.hu.
Ágnes KittelInstitute of Experimental Medicine, Hungarian Academy of Sciences, H-1450, Budapest, Hungary. kittel@koki.hu.
Norbert ImreDepartment of Medical Chemistry, University of Szeged, H-6720 Szeged, Hungary. imre.norbert@med.u-szeged.hu.
Tamás A MartinekDepartment of Medical Chemistry, University of Szeged, H-6720 Szeged, Hungary. martinek.tamas@med.u-szeged.hu.
Csaba PálSynthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary. pal.csaba@brc.mta.hu.
Piroska Szabó-RévészDepartment of Pharmaceutical Technology, University of Szeged, H-6720 Szeged, Hungary. revesz@pharm.u-szeged.hu.
Mária A DeliInstitute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, H-6726, Szeged, Hungary. deli.maria@brc.mta.hu.
University of Szeged · HUHUN-REN Szegedi Biológiai Kutatóközpont · HUGedeon Richter (Hungary) · HUHUN-REN Institute of Experimental Medicine · HU

Funding

Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal GINOP-2.2.1-15-2016-00007
6 · The paper itself

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.

Indexed as

absorption enhancerantimicrobial peptideCaco-2cell-penetrating peptide (CPP)claudindrug deliveryintestinal epithelial cellsKLALPN159tight junction modulator

Identifiers

PMID30744154
PMCPMC6410202
OpenAlexW2914891586

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.