Synergistic effects of antimicrobial peptide dendrimer-chitosan polymer conjugates against Pseudomonas aeruginosa.

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Authors
Date

March 15, 2022

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Serveur académique Lausannois

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This document is linked to :
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.carbpol.2021.119025

This document is linked to :
info:eu-repo/semantics/altIdentifier/pmid/35027127

This document is linked to :
info:eu-repo/semantics/altIdentifier/eissn/1879-1344

This document is linked to :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_40DB7D6879C51

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Serveur Académique Lausannois

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Université de Lausanne et CHUV

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info:eu-repo/semantics/openAccess , CC BY-NC-ND 4.0 , https://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords 0

Animals; Anti-Bacterial Agents/chemistry; Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/toxicity; Antimicrobial Peptides/chemistry; Antimicrobial Peptides/pharmacology; Antimicrobial Peptides/toxicity; Cell Membrane/drug effects; Cells, Cultured; Chitosan; Dendrimers; Drug Synergism; Hemolysis; Humans; Microbial Sensitivity Tests; Polymers; Pseudomonas aeruginosa/drug effects; Antimicrobial formulations; Antimicrobial peptide dendrimers (AMPDs); Multidrug-resistant bacteria; Synergistic antimicrobial activities; Wound infections

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Dendritic compounds

Cite this document

V. Patrulea et al., « Synergistic effects of antimicrobial peptide dendrimer-chitosan polymer conjugates against Pseudomonas aeruginosa. », Serveur académique Lausannois, ID : 10.1016/j.carbpol.2021.119025

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Abstract 0

We report herein a new chemical platform for coupling chitosan derivatives to antimicrobial peptide dendrimers (AMPDs) with different degrees of ramification and molecular weights via thiol-maleimide reactions. Previous studies showed that simple incorporation of AMPDs to polymeric hydrogels resulted in a loss of antibacterial activity and augmented cytotoxicity to mammalian cells. We have shown that coupling AMPDs to chitosan derivatives enabled the two compounds to act synergistically. We showed that the antimicrobial activity was preserved when incorporating AMPD conjugates into various biopolymer formulations, including nanoparticles, gels, and foams. Investigating their mechanism of action using electron and time-lapse microscopy, we showed that the AMPD-chitosan conjugates were internalized after damaging outer and inner Gram-negative bacterial membranes. We also showed the absence of AMPD conjugates toxicity to mammalian cells. This chemical technological platform could be used for the development of new membrane disruptive therapeutics to eradicate pathogens present in acute and chronic wounds.

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