Colistin sulfate-sodium deoxycholate sulfate micelle formulations; molecular interactions, cell nephrotoxicity and bioactivity

Abstract

This study aimed to develop a micelle formulation of colistin with several mole ratios of sodium deoxycholate sulfate (SDCS) carrier to reduce its nephrotoxicity. The molar ratio and surface properties of colistin and SDCS were determined. Colistin was incorporated into SDCS micelles followed by lyophilisation. The formulated micelles were evaluated in terms of particle size, zeta potential, morphology, thermal properties, encapsulation efficiency (EE) and release profile. The interactions were analysed with FTIR, NMR and also in-silico studies using molecular docking. The MIC and MBC were calculated, while time-kill kinetics were observed. Furthermore, a cytotoxicity study of the formulations against kidney cells was carried out and data were analysed. Particle sizes were in the range of 140.9–162.6 nm with spherical shapes, and the zeta potential values were between −35.3 and −22.8 mV. The EE of colistin was between 17.73 and 40.15%. FTIR and DSC data indicated an interaction between the colistin and SDCS, and the NMR analysis revealed hydrogen bonding and electrostatic interaction as the main interaction. Molecular docking simulation showed that multiple hydrogen bonds were present between the hydrophilic ring of colistin and SDCS. The formulations showed good safety profiles with non-cytotoxic effects against the kidney cell while maintaining antibacterial activity. The overall results indicated that micelle formulations with SDCS can be a good option for the delivery of colistin to reduce its nephrotoxicity with better antibacterial activity, while further studies in the animal model are important.