Conjugates of Chitosan with β-Cyclodextrins as Promising Carriers for the Delivery of Levofloxacin: Spectral and Microbiological Studies

Abstract

In this work, we synthesized chitosan 5 kDa conjugates with β-cyclodextrins with various substituents as promising mucoadhesive carriers for the delivery of fluoroquinolones using the example of levofloxacin. The obtained conjugates were comprehensively characterized by spectral methods (UV-Vis, ATR-FTIR, 1H NMR, SEM). The physico-chemical properties of the complex formations were studied by IR, UV, and fluorescence spectroscopy. The dissociation constants of complexes with levofloxacin were determined. Complexation with conjugates provided four times slower drug release in comparison with plain CD and more than 20 times in comparison with the free drug. The antibacterial activity of the complexes was tested on model microorganisms Gram-negative bacteria Escherichia coli ATCC 25922 and Gram-positive Bacillus subtilis ATCC 6633. The complex with the conjugate demonstrated the same initial levofloxacin antibacterial activity but provided significant benefits, e.g., prolonged release.

Cyclodextrins and Their Polymers Affect Human Serum Albumin’s Interaction with Drugs Used in the Treatment of Pulmonary Infections

“…We determined the minimum inhibition concentration (MIC) by the agar well diffusion method [ 25 , 26 , 27 ]. The cell’s suspension (overnight Escherichia coli ATCC 25,922 (grown in Luria Bertuni medium for 12 h)) was diluted to 0.5 McFarland standard.…”

Combined System for the Simultaneous Delivery of Levofloxacin and Rifampicin: Structural and Functional Properties and Antibacterial Activity

“…Mono-(6-(hexamethylenediamine)-6-deoxy)-β-cyclodextrin (NH 2 -CD), 2-hydroxy propyl-β-cyclodextrin (HP-CD), 5 kDa Chitosan oligosaccharide lactate with deacetylation degree 98% (Chit), levofloxacin and rifampicin were obtained from Sigma Aldrich (St. Louis, MO, USA); tablets of phosphate-buffered saline and HCl were obtained from "PanEco" (Moscow, Russia); dipalmitoylphosphatidylcholine, sodium salt and 16:0 cardiolipin 1 ,3bis-[1,2-dipalmitoyl-sn -glycero-3-phospho]-glycerol were obtained from "Avanti Polar Lipids" (Alabaster, AL, USA); dialysis bags with a cut-off molecular weight of 12-14 kDa were obtained from "Orange Scientific" (Braine-l'Alleud, Belgium); and dialysis bags with a cut-off molecular weight of 3,5 kDa were obtained from "Serva" (Heidelberg, Germany). NH 2 -CD-Chit and HP-CD-Chit were synthetized and purified according to the methodic [15] and used in this research without additional treatment.…”

“…Sampling with a volume of 100 µL was carried out during the day, maintaining a constant volume of the external solution. We obtained points of 5,10,15,30,45,60,75,90,120,150,180,210,240,270,300, 960 and 1440 min. Samples were analyzed through UV spectroscopy to determine the proportion of the drug released.…”

“…According to the European Medicines Agency (2014) ("Background review for cyclodextrins used as excipient" (EMA/CHMP/333892/2013)) betacyclodextrins with maximum applicable volume of 10% provide excellent tolerance via nasal mucosa, which was demonstrated in irritation studies with rabbits that did not show any local or systemic toxic effects from nasal administration for 3 months. However, such small complexes are not suitable for inhaled delivery, and thus, we synthetized a polymer-based carrier of low-molecular-based chitosan conjugated with β-cyclodextrin tori [15]. This carrier provides high encapsulation efficacy and a suitable release profile.…”

Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Properties

“…We determined the minimum inhibition concentration (MIC) using the agar well diffusion method [19][20][21]. The cell suspension of overnight-cultured Escherichia coli (ATCC 25922) and Bacillus subtilis (ATCC 6633) (grown in the Luria-Bertuni medium for 12 h) was diluted to a 0.5 McFarland standard.…”