Encapsulation of sulfamethazine drug by β-cyclodextrins and its adsorption on carbon nanotubes

Abstract

Sulfonamides are preventive and therapeutic agents for certain infections caused by gram-positive and gram-negative microorganisms. At the same time, their widespread application is hindered by their low solubility in aqueous media. Since the water solubility of sulfonamide drugs is increased in the presence of cyclodextrins, the host-guest type complex formation of these antibiotics with cyclodextrins is an extensively studied field. Sulfamethazine is a representative member of the sulfonamide antibiotic drugs, it is still used in human and veterinary therapy. Previous studies described the ability of -cyclodextrin to increase the solubility of this drug in aqueous solution and studied the structure of the complexes by experimental and molecular modeling techniques. This work aims to examine the interactions of sulfamethazine with two β-cyclodextrin derivatives at different pH in the temperature range of 298-313 K. Results showed the formation of stable complexes of sulfamethazine with both native and randomly methylated β-cyclodextrin host molecules. Spectroscopic measurements and molecular modeling studies indicated the possible driving forces (hydrophobic interaction, hydrogen bonding, and electrostatic interaction) of the complex formation, and highlighted the importance of the reorganization of the solvent molecules during the entering of the guest molecule into the host’s cavity. Functionalization of the β-cyclodextrin molecule does not affect considerably the complex stabilities, therefore the native β-cyclodextrin molecule looks the simplest and most effective inclusion host to design a selective and sensitive tool for sulfamethazine detection. The protonation state of this drug affects not only its aqueous solubility but controls its inclusion complexes with -cyclodextrins. The pH-affected structures of the complexes explain previous contradictory findings based on the inclusion of the aniline moiety as well as the pyrimidine ring through the cyclodextrin cavity. Furthermore, surprisingly, the interaction between the neutral and anionic forms of the guest molecule and cyclodextrins with electron rich cavity is thermodynamically more favorable compared to the cationic guest. This property probably due to the enhanced formation of the zwitterionic form of sulfamethazine in the hydrophobic cavities of cyclodextrins, which affect significantly the stability of sulfamethazine - cyclodextrin complexes. Since sulfonamide antibiotics, including sulfamethazine, are poorly metabolized, they can be found in surface water, in wastewater and in meat-producing animals with considerable concentrations. Therefore, several studies have focused on the sulfonamide drugs adsorption on different kinds of natural and synthetic materials to remove them from the environment. Accordingly, in this work, the removal of sulfamethazine from water has also been tested. Based on the interaction between sulfamethazine and -cyclodextrin, a cyclodextrin containing insoluble polymer has been tested to extract sulfamethazine from aqueous solution. Furthermore, carbon nanotubes, successfully used for the adsorption of several antibiotics earlier, have also been investigated as possible sorbents to eliminate this drug from aqueous solution. Systematic analysis has been done to describe the effect of the number of layers of walls and the effect of the functionalization of the carbon nanotubes. Results showed that although insoluble -cyclodextrin bead polymer is not applicable for removing sulfamethazine from aqueous solution effectively, single-walled carbon nanotubes are suitable for extracting this antibiotic from aqueous media. These observations might be relevant for the preparation of orally administered products of sulfonamide-cyclodextrin complexes which can be useful in finding materials suitable for developing new sulfonamide drug binders to remove these drugs from contaminated beverages, e.g. from drink water.