نبذة مختصرة : Doctor of Philosophy (Pharmaceutical Sciences), 2023 ; Colistin is still used in multidrug-resistant gram-negative bacteria (MDR-GNB) therapy but the nephrotoxicity and neurotoxicity still become a major setback for its clinical use. Sodium deoxycholate sulfate (SDCS) carrier is used in micelle formulation with colistin to mitigate the known toxicity of colistin. The surface property of colistin and SDCS were evaluated before formulation with the lyophilisation technique. Several physicochemical parameters were evaluated like particle size, zeta potential, morphology, encapsulation efficiency (EE) and release profile. The chemical interactions were analysed using FTIR, NMR and molecular docking. The cytotoxicity of formulations was tested with different kidney cell lines. The in vivo toxicity was carried out in male mice C57BL/6 with colistin and colistin formulation for 7 consecutive days. The physiological changes were observed and measured after treatment. The serum biomarkers were measured including blood urea nitrogen (BUN), creatinine (Cr), superoxide dismutase (SOD), and catalase (CAT). Histopathological alterations in mice organs were analysed. The hydrodynamic diameters of the formulation were in the range of 140 to 170 nm with a spherical shape and negative zeta potential between −35.3 and −22.8 mV. The EE of formulations were between 70 and 76.4% with slower release measured compared to colistin. Molecular interactions were determined from FTIR and NMR spectra. Molecular docking simulation showed that multiple hydrogen bonds were present between the hydrophilic ring of colistin and SDCS. The colistin:SDCS formulations improved the thermal sensitivity of the mice compared to the control group. The BUN and Cr results showed no significant kidney dysfunction; however, the oxidative stress biomarkers decreased in the colistin with a lesser decrease in colistin-SDCS treated mice. Several histological alterations were observed in the kidney, liver, spleen, and sciatic nerve tissues following colistin ...
No Comments.