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

The therapy of resistant forms of tuberculosis requires the simultaneous use of several drugs, in particular, a combination of rifampicin and levofloxacin. In this paper, we aimed to design a combined system for the simultaneous delivery of these drugs for potential inhalation administration. A feature of this system is the incorporation of rifampicin into optimized liposomal vesicles capable of forming a multipoint non-covalent complex with chitosan-ß-cyclodextrin conjugates. Levofloxacin is incorporated into cyclodextrin tori by forming a host-guest complex. Here, a comprehensive study of the physicochemical properties of the obtained systems was carried out and special attention was paid to the kinetics of cargo release for individual drugs and in the combined system. The release of levofloxacin in combined system is slow and is described by the Higuchi model in all cases. The release of rifampicin from liposomes during the formation of complexes with polymeric conjugates is characterized by the change of the Higuchi model to the Korsmeyer-Peppas model with the main type of diffusion against Fick's law. Microbiological studies in solid and liquid growth media a consistently high antibacterial activity of the obtained systems was shown against B. subtilis and E. coli.

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

In this work, we synthesized chitosan 5 kDa conjugates with ß-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.