Abstract
The aim of this study was to improve the solubility, antibiofilm activity and safety profile of chloramphenicol (CP) by the preparation of multicomponent complexes with γ-cyclodextrin (γ-CD) and N-acetylcysteine (NAC). The phase solubility and isothermal titration calorimetry (ITC) studies suggested the complex formation and revealed the solubility of CP is enhanced during the complexation. The most important driving forces of the formation of the complexes were determined by molecular modeling techniques and ITC. Complexation evidence was also provided by data from NMR experiments. The solid-state materials were prepared by physical mixture and freeze-drying methods and subjected to physicochemical characterization using scanning electron microscopy, electron probe microanalysis, thermoanalytical methods and powder X-Ray diffraction. The ability of the materials to decrease the cellular activity of Staphylococcus aureus biofilms was studied by XTT assay. Furthermore, reactive oxygen species determination by chemiluminescence was used to assess the effect of complexation on drug toxicity in human leukocytes. The results obtained allowed us to conclude that the formation of multicomponent complexes of CP with γ-CD and NAC is an effective pharmaceutical strategy that can enhance the physicochemical and biological properties of this antibacterial drug.
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