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Modification of Dispersin B with Cyclodextrin-Ciprofloxacin Derivatives for Treating Staphylococcal
To address the high tolerance of biofilms to antibiotics, it is urgent to develop new strategies to fight against these bacterial consortia. An innovative antibiofilm nanovector drug delivery system, consisting of Dispersin B-permethylated-β-cyclodextrin/ciprofloxacin adamantyl (DspB-β-CD/CIP-Ad), i...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10386341/ https://www.ncbi.nlm.nih.gov/pubmed/37513185 http://dx.doi.org/10.3390/molecules28145311 |
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author | Abdelkader, Jinan Alelyani, Magbool Alashban, Yazeed Alghamdi, Sami A. Bakkour, Youssef |
author_facet | Abdelkader, Jinan Alelyani, Magbool Alashban, Yazeed Alghamdi, Sami A. Bakkour, Youssef |
author_sort | Abdelkader, Jinan |
collection | PubMed |
description | To address the high tolerance of biofilms to antibiotics, it is urgent to develop new strategies to fight against these bacterial consortia. An innovative antibiofilm nanovector drug delivery system, consisting of Dispersin B-permethylated-β-cyclodextrin/ciprofloxacin adamantyl (DspB-β-CD/CIP-Ad), is described here. For this purpose, complexation assays between CIP-Ad and (i) unmodified β-CD and (ii) different derivatives of β-CD, which are 2,3-O-dimethyl-β-CD, 2,6-O-dimethyl-β-CD, and 2,3,6-O-trimethyl-β-CD, were tested. A stoichiometry of 1/1 was obtained for the β-CD/CIP-Ad complex by NMR analysis. Isothermal Titration Calorimetry (ITC) experiments were carried out to determine Ka, ΔH, and ΔS thermodynamic parameters of the complex between β-CD and its different derivatives in the presence of CIP-Ad. A stoichiometry of 1/1 for β-CD/CIP-Ad complexes was confirmed with variable affinity according to the type of methylation. A phase solubility study showed increased CIP-Ad solubility with CD concentration, pointing out complex formation. The evaluation of the antibacterial activity of CIP-Ad and the 2,3-O-dimethyl-β-CD/CIP-Ad or 2,3,6-O-trimethyl-β-CD/CIP-Ad complexes was performed on Staphylococcus epidermidis (S. epidermidis) strains. The Minimum Inhibitory Concentration (MIC) studies showed that the complex of CIP-Ad and 2,3-O-dimethyl-β-CD exhibited a similar antimicrobial activity to CIP-Ad alone, while the interaction with 2,3,6-O-trimethyl-β-CD increased MIC values. Antimicrobial assays on S. epidermidis biofilms demonstrated that the synergistic effect observed with the DspB/CIP association was partly maintained with the 2,3-O-dimethyl-β-CDs/CIP-Ad complex. To obtain this “all-in-one” drug delivery system, able to destroy the biofilm matrix and release the antibiotic simultaneously, we covalently grafted DspB on three carboxylic permethylated CD derivatives with different-length spacer arms. The strategy was validated by demonstrating that a DspB-permethylated-β-CD/ciprofloxacin-Ad system exhibited efficient antibiofilm activity. |
format | Online Article Text |
id | pubmed-10386341 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103863412023-07-30 Modification of Dispersin B with Cyclodextrin-Ciprofloxacin Derivatives for Treating Staphylococcal Abdelkader, Jinan Alelyani, Magbool Alashban, Yazeed Alghamdi, Sami A. Bakkour, Youssef Molecules Article To address the high tolerance of biofilms to antibiotics, it is urgent to develop new strategies to fight against these bacterial consortia. An innovative antibiofilm nanovector drug delivery system, consisting of Dispersin B-permethylated-β-cyclodextrin/ciprofloxacin adamantyl (DspB-β-CD/CIP-Ad), is described here. For this purpose, complexation assays between CIP-Ad and (i) unmodified β-CD and (ii) different derivatives of β-CD, which are 2,3-O-dimethyl-β-CD, 2,6-O-dimethyl-β-CD, and 2,3,6-O-trimethyl-β-CD, were tested. A stoichiometry of 1/1 was obtained for the β-CD/CIP-Ad complex by NMR analysis. Isothermal Titration Calorimetry (ITC) experiments were carried out to determine Ka, ΔH, and ΔS thermodynamic parameters of the complex between β-CD and its different derivatives in the presence of CIP-Ad. A stoichiometry of 1/1 for β-CD/CIP-Ad complexes was confirmed with variable affinity according to the type of methylation. A phase solubility study showed increased CIP-Ad solubility with CD concentration, pointing out complex formation. The evaluation of the antibacterial activity of CIP-Ad and the 2,3-O-dimethyl-β-CD/CIP-Ad or 2,3,6-O-trimethyl-β-CD/CIP-Ad complexes was performed on Staphylococcus epidermidis (S. epidermidis) strains. The Minimum Inhibitory Concentration (MIC) studies showed that the complex of CIP-Ad and 2,3-O-dimethyl-β-CD exhibited a similar antimicrobial activity to CIP-Ad alone, while the interaction with 2,3,6-O-trimethyl-β-CD increased MIC values. Antimicrobial assays on S. epidermidis biofilms demonstrated that the synergistic effect observed with the DspB/CIP association was partly maintained with the 2,3-O-dimethyl-β-CDs/CIP-Ad complex. To obtain this “all-in-one” drug delivery system, able to destroy the biofilm matrix and release the antibiotic simultaneously, we covalently grafted DspB on three carboxylic permethylated CD derivatives with different-length spacer arms. The strategy was validated by demonstrating that a DspB-permethylated-β-CD/ciprofloxacin-Ad system exhibited efficient antibiofilm activity. MDPI 2023-07-10 /pmc/articles/PMC10386341/ /pubmed/37513185 http://dx.doi.org/10.3390/molecules28145311 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Abdelkader, Jinan Alelyani, Magbool Alashban, Yazeed Alghamdi, Sami A. Bakkour, Youssef Modification of Dispersin B with Cyclodextrin-Ciprofloxacin Derivatives for Treating Staphylococcal |
title | Modification of Dispersin B with Cyclodextrin-Ciprofloxacin Derivatives for Treating Staphylococcal |
title_full | Modification of Dispersin B with Cyclodextrin-Ciprofloxacin Derivatives for Treating Staphylococcal |
title_fullStr | Modification of Dispersin B with Cyclodextrin-Ciprofloxacin Derivatives for Treating Staphylococcal |
title_full_unstemmed | Modification of Dispersin B with Cyclodextrin-Ciprofloxacin Derivatives for Treating Staphylococcal |
title_short | Modification of Dispersin B with Cyclodextrin-Ciprofloxacin Derivatives for Treating Staphylococcal |
title_sort | modification of dispersin b with cyclodextrin-ciprofloxacin derivatives for treating staphylococcal |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10386341/ https://www.ncbi.nlm.nih.gov/pubmed/37513185 http://dx.doi.org/10.3390/molecules28145311 |
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