Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

An Antibiofilm Vector Based on a Modified β-Cyclodextrin: Complexation Study and Biological Activity

Version 1 : Received: 30 April 2023 / Approved: 1 May 2023 / Online: 1 May 2023 (10:22:03 CEST)

A peer-reviewed article of this Preprint also exists.

Abdelkader, J.; Alelyani, M.; Alashban, Y.; Alghamdi, S.A.; Bakkour, Y. Modification of Dispersin B with Cyclodextrin-Ciprofloxacin Derivatives for Treating Staphylococcal. Molecules 2023, 28, 5311. Abdelkader, J.; Alelyani, M.; Alashban, Y.; Alghamdi, S.A.; Bakkour, Y. Modification of Dispersin B with Cyclodextrin-Ciprofloxacin Derivatives for Treating Staphylococcal. Molecules 2023, 28, 5311.

Abstract

To face the high tolerance of biofilms to antibiotics, it is urgent to develop new strategies to fight against these bacterial consortia. We describe here an innova-tive antibiofilm nano vector, consisting of a Dispersin B-permethylated-β-cyclodextrin/ciprofloxacin adamantly (DspB-β-CD/CIP-Ad). For this purpose, complexation assays between CIP-Ad and (i) unmodified β-CD and (ii) different derivatives of β-CD, that 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. ITC experiments were carried out to determine Ka, ΔH, ΔS thermodynamic parameters of the complex between β-CD or its different derivatives in the presence of CIP-Ad. A stoichiometry 1/1 of β-CD/CIP-Ad complexes was confirmed with variable affinity according to the type of methylation. A phase solubility study showed increased CIP-Ad solubili-ty with CDs 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 S.epidermidis strains. MIC studies showed that the complex of CIP-Ad and 2,3-O-dimethyl-β-CD exhibited 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" nano vector, 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 nanovector exhibited efficient antibiofilm activity.

Keywords

Cyclodextrin; Ciprofloxacin; Dispersin B; Inclusion complex; Antibiofilm

Subject

Chemistry and Materials Science, Organic Chemistry

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