Transportan 10 improves the pharmacokinetics and pharmacodynamics of vancomycin

Jarosław Ruczyński , Izabela Rusiecka , Katarzyna Turecka , Agnieszka Kozłowska , Magdalena Alenowicz , Iwona Gągało , Anna Kawiak , Piotr Rekowski , Krzysztof Waleron , Ivan Kocić

Abstract

In the presented study, transportan 10 (TP10), an amphipathic cell penetrating peptide (CPP) with high translocation activity, was conjugated with vancomycin (Van), which is known for poor access to the intracellular bacteria and the brain. The antibacterial activity of the conjugates was tested on selected clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus sp. It turned out that all of them had superior antimicrobial activity in comparison to that of free Van, which became visible particularly against clinical MRSA strains. Furthermore, one of the conjugates was tested against MRSA - infected human cells. With respect to them, this compound showed high bactericidal activity. Next, the same conjugate was screened for its capacity to cross the blood brain barrier (BBB). Therefore, qualitative and quantitative analyses of the conjugate's presence in the mouse brain slices were carried out after its iv administration. They indicated the conjugate's presence in the brain in amount >200 times bigger than that of Van. The conjugates were safe with respect to erythrocyte toxicity (erythrocyte lysis assay). Van in the form of a conjugate with TP10 acquires superior pharmacodynamic and pharmacokinetic.
Author Jarosław Ruczyński (FCh / DMB / LChBAC)
Jarosław Ruczyński,,
- Laboratory of Chemistry of Biologically Active Compounds
, Izabela Rusiecka
Izabela Rusiecka,,
-
, Katarzyna Turecka
Katarzyna Turecka,,
-
, Agnieszka Kozłowska (FCh / DMB / LChBAC)
Agnieszka Kozłowska,,
- Laboratory of Chemistry of Biologically Active Compounds
, Magdalena Alenowicz (FCh / DMB / LChBAC)
Magdalena Alenowicz,,
- Laboratory of Chemistry of Biologically Active Compounds
, Iwona Gągało
Iwona Gągało,,
-
, Anna Kawiak (IFB / IB / DBiotech)
Anna Kawiak,,
- Department of Biotechnology
, Piotr Rekowski (FCh / DMB / LChBAC)
Piotr Rekowski,,
- Laboratory of Chemistry of Biologically Active Compounds
, Krzysztof Waleron
Krzysztof Waleron,,
-
, Ivan Kocić
Ivan Kocić,,
-
Journal seriesScientific Reports, ISSN 2045-2322, (A 40 pkt)
Issue year2019
Vol9
Pages1-15
Publication size in sheets0.7
ASJC Classification1000 Multidisciplinary
DOIDOI:10.1038/s41598-019-40103-w
URL https://www.nature.com/articles/s41598-019-40103-w.pdf
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)40
ScoreMinisterial score = 40.0, 04-04-2019, ArticleFromJournal
Ministerial score (2013-2016) = 40.0, 04-04-2019, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.401; WoS Impact Factor: 2017 = 4.122 (2) - 2017=4.609 (5)
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