Physical and Chemical Properties of the Guest–Host Inclusion Complexes of Cyprofloxacin with β-Cyclodextrin Derivatives

Skuredina, Anna A.; Kopnova, Tatiana Yu.; Le-Deygen, Irina M.; Kudryashova, Еlena V.

doi:10.3103/s0027131420040069

Cited by 11 publications

(10 citation statements)

References 29 publications

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“…Promising approaches to the treatment of diseases, where the driver or direct participants are macrophages, imply targeted and prolonged release of drugs to reduce the dose and frequency of taking the drug. Simple cyclodextrins form inclusion complexes with fluoroquinolones with constants 10 3 –10 4 M [ 72 , 73 , 74 ], which does not lead to a noticeable effect of prolonged release [ 75 ]. Therefore, molecular systems are being developed that can retain drugs with greater affinity, for example, polymer meshes of cross-linked cyclodextrins that increase the effective release of the drug up to 1–5 days [ 40 ].…”

Section: Resultsmentioning

confidence: 99%

Spectroscopy Approach for Highly-Efficient Screening of Lectin-Ligand Interactions in Application for Mannose Receptor and Molecular Containers for Antibacterial Drugs

Zlotnikov

Kudryashova

2022

Pharmaceuticals

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Rational search of a ligand for a specific receptor is a cornerstone of a typical drug discovery process. However, to make it more “rational” one would appreciate having detailed information on the functional groups involved in ligand-receptor interaction. Typically, the 3D structure of a ligand-receptor complex can be built on the basis of time-consuming X-ray crystallography data. Here, a combination of FTIR and fluorescence methods, together with appropriate processing, yields valuable information about the functional groups of both the ligand and receptor involved in the interaction, with the simplicity of conventional spectrophotometry. We have synthesized the “molecular containers” based on cyclodextrins, polyethyleneimines (PEI) or spermine with mannose-rich side-chains of different molecular architecture (reticulated, star-shaped and branched) with variable parameters to facilitate delivery to alveolar macrophages. We have shown that synthetic mannose-rich conjugates are highly affine to the model mannose receptor ConA: Kd ≈ 10−5–10−7 M vs. natural ligand trimannoside (10−5 M). Further, it was shown that molecular containers effectively load levofloxacin (dissociation constants are 5·10−4–5·10−6 M) and the eugenol adjuvant (up to 15–80 drug molecules for each conjugate molecule) by including them in the cyclodextrins cavities, as well as by interacting with polymer chains. Promising formulations of levofloxacin and its enhancer (eugenol) in star-shaped and polymer conjugates of high capacity were obtained. UV spectroscopy demonstrated a doubling of the release time of levofloxacin into the external solution from the complexes with conjugates, and the effective action time (time of 80% release) was increased from 0.5 to 20–70 h. The synergy effect of antibacterial activity of levofloxacin and its adjuvants eugenol and apiol on Escherichia coli was demonstrated: the minimum effective concentration of the antibiotic was approximately halved.

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Section: Resultsmentioning

confidence: 99%

Spectroscopy Approach for Highly-Efficient Screening of Lectin-Ligand Interactions in Application for Mannose Receptor and Molecular Containers for Antibacterial Drugs

Zlotnikov

Kudryashova

2022

Pharmaceuticals

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“…Complexation between FQ and CD occurs due to the immersion of the aromatic backbone of the drug molecule into the CD cavity, while the piperazine fragment, positively charged at pH 7.4, remains outside [6], and the carboxyl group becomes less accessible for interaction with other ligands. In the complexation of FQ with CD, the morpholine fragment in the drug structure promotes more complete immersion of the drug molecule into the CD cavity than in the case of CF.…”

Section: Resultsmentioning

confidence: 99%

“…CDs and their derivatives are of great interest to the pharmaceutical industry. They help to increase the solubility [6,7], bioavailability and stability of drugs, reduce toxicity, and allow varying the pharmacokinetic properties of biologically active molecules [1,8]. Despite the widespread use of drug formulations based on CDs, the interaction of complexes with biological substances requires more detailed consideration.…”

Section: Introductionmentioning

confidence: 99%

Effect of Methyl-β-Cyclodextrin on the Interaction of Fluoroquinolones with Human Serum Albumin

et al. 2022

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Abstract— The influence of the structure of fluoroquinolones (on the example of ciprofloxacin and levofloxacin) and their complexation with methyl-β-cyclodextrin on the interaction of the drug with human serum albumin was studied. It was found that the binding of the drug molecule with albumin is significantly affected by the structure of fluoroquinolone, as well as the presence of methyl-β-cyclodextrin. It was discovered that of the two fluoroquinolones, the more hydrophobic ciprofloxacin molecule interacts more strongly with the protein, using circular dichroism and fluorescence spectroscopy methods. It has also been shown that binding of albumin to the drug causes quenching of protein fluorescence, and this effect is more pronounced for ciprofloxacin. The complexation of fluoroquinolones with methyl-β-cyclodextrin leads to a change in the interaction of fluoroquinolones with the protein: in the case of complexes, more pronounced interactions are observed for levofloxacin. The results obtained will help to bring the use of fluoroquinolones to a new level in clinical practice, by creating new highly effective drugs with improved properties.

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“…The hydrophobic cavity enables CDs to encapsulate hydrophobic drug molecules (or their fragments), forming non-covalent inclusion guest–host complexes. Complex formation leads to the improvement of the drug’s physico-chemical properties, namely the increase in its solubility, stability and bioavailability [ 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrins and Their Polymers Affect the Lipid Membrane Permeability and Increase Levofloxacin’s Antibacterial Activity In Vitro

et al. 2022

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Cyclodextrins (CDs) are promising drug carriers that are used in medicine. We chose CDs with different substituents (polar/apolar, charged/neutral) to obtain polymers (CDpols) with different properties. CDpols are urethanes with average Mw of ~120 kDa; they form nanoparticles 100–150 nm in diameter with variable ζ-potential. We studied the interaction of CD and CDpols with model (liposomal) and bacterial membranes. Both types of CD carriers cause an increase in the liposomal membrane permeability, and for polymers, this effect was almost two times stronger. The formation of CD/CDpols complexes with levofloxacin (LV) enhances LV’s antibacterial action 2-fold in vitro on five bacterial strains. The most pronounced effect was determined for LV-CD complexes. LV-CDs and LV-CDpols adsorb on bacteria, and cell morphology influences this process dramatically. According to TEM studies, the rough surface and proteinaceous fimbria of Gram-negative E. coli facilitate the adsorption of CD particles, whereas the smooth surface of Gram-positive bacteria impedes it. In comparison with LV-CDs, LV-CDpols are adsorbed 15% more effectively by E. coli, 2.3-fold better by lactobacilli and 5-fold better in the case of B. subtilis. CDs and CDpols are not toxic for bacterial cells, but may cause mild defects that, in addition to LV-CD carrier adsorption, improve LV’s antibacterial properties.

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Physical and Chemical Properties of the Guest–Host Inclusion Complexes of Cyprofloxacin with β-Cyclodextrin Derivatives

Cited by 11 publications

References 29 publications

Spectroscopy Approach for Highly-Efficient Screening of Lectin-Ligand Interactions in Application for Mannose Receptor and Molecular Containers for Antibacterial Drugs

Spectroscopy Approach for Highly-Efficient Screening of Lectin-Ligand Interactions in Application for Mannose Receptor and Molecular Containers for Antibacterial Drugs

Effect of Methyl-β-Cyclodextrin on the Interaction of Fluoroquinolones with Human Serum Albumin

Cyclodextrins and Their Polymers Affect the Lipid Membrane Permeability and Increase Levofloxacin’s Antibacterial Activity In Vitro

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