Please use this identifier to cite or link to this item: http://kb.psu.ac.th/psukb/handle/2016/19259
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dc.contributor.advisorTeerapol Srichana-
dc.contributor.authorBintang, Muhammad Ali Khumaini Mudhar-
dc.date.accessioned2023-12-20T09:09:33Z-
dc.date.available2023-12-20T09:09:33Z-
dc.date.issued2023-
dc.identifier.urihttp://kb.psu.ac.th/psukb/handle/2016/19259-
dc.descriptionDoctor of Philosophy (Pharmaceutical Sciences), 2023en_US
dc.description.abstractColistin 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 treatment, whereas less evidence of toxicity with colistin-SDCS. The overall results indicated that micelle formulations with SDCS showed safer for kidney and nerve cells while maintaining the antibacterial activity of colistin. This study revealed the potential for colistin development with SDCS for safer clinical use against MDR-GNB.en_US
dc.language.isoenen_US
dc.publisherPrince of Songkla Universityen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Thailand*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/th/*
dc.subjectColistinen_US
dc.subjectSodium deoxycholate sulfateen_US
dc.subjectMicellesen_US
dc.subjectNephrotoxicityen_US
dc.subjectNeurotoxicityen_US
dc.subjectMolecular dockingen_US
dc.subjectHistopathology.en_US
dc.titleFormulation optimization and characterization of colistin using sodium deoxycholate sulfate for intravenous administrationen_US
dc.typeThesisen_US
dc.contributor.departmentFaculty of Pharmaceutical Sciences (Pharmaceutical Technology)-
dc.contributor.departmentคณะเภสัชศาสตร์ ภาควิชาเทคโนโลยีเภสัชกรรม-
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