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.

This study investigates the influence of positional isomerism on the physicochemical characteristics of polymeric matrices by examining polyo-anisidine (POA) and polyp-anisidine (PPA) in conjunction with TiO₂ nanoparticles. The synthesis of POA@TiO₂ and PPA@TiO₂ involved chemical oxidative polymerization. X-ray diffraction analysis revealed the anatase structure of TiO₂ nanoparticles. Transmission electron microscopy confirmed the successful integration of TiO₂ nanoparticles within the polymer matrix. Moreover, FTIR and UV–Vis spectroscopy confirmed the effective interaction between the nanoparticle and the polymer. TGA indicated that POA@TiO₂ exhibited a lower weight loss than PPA@TiO₂, suggesting an enhancement in thermal stability. Although the incorporation of TiO₂ nanoparticles led to a reduction in the electrical conductivity of the pristine polymers (PPA and POA), the resultant nanocomposites retained high conductivities within the range of 0.08 to 0.34 S.cm⁻¹. Furthermore, the POA-based polymer matrix displayed promising electrochemical properties. Significantly, the adherence of the POA layer to TiO₂ nanoparticles suggests potential practical applications.

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.