Assessment of Polymyxin B with Sodium Deoxycholate Sulfate Micelles in a Rat Model to Combat Polymyxin Nephrotoxicity

TL;DR

This study explores using a new formulation to reduce kidney damage caused by a common antibiotic in rats.

Contribution

A novel SDCS micelle formulation is proposed to reduce nephrotoxicity of polymyxin B in a rat model.

Findings

PMB-SDCS formulations improved serum biomarker measurements and reduced kidney toxicity.

Molecular docking showed SDCS reduces PMB binding to human serum albumin.

PMB-SDCS formulations caused less acute toxicity and less PMB accumulation in kidneys.

Abstract

Background/Objectives: Polymyxin B (PMB) was incorporated into a sodium deoxycholate sulfate (SDCS) micelle formulation to mitigate polymyxin-induced nephrotoxicity. This study examined the effect of the formulation on nephrotoxicity and biodistribution in a rat model. Methods: Four groups of rats were subcutaneously administered one of the following: normal saline, SDCS, PMB, or a PMB-SDCS formulation. After treatment, the weight changes were recorded, and the rats were euthanized to collect blood for serum biochemistry measurements. The histopathological damage to organs was examined. Two additional groups of rats received the same dose of PMB and the PMB-SDCS formulation subcutaneously; however, their serum PMB was measured at predetermined time points, and the PMB concentrations in the organs were measured. Molecular docking for PMB and formulation with human serum albumin was also performed. Results: The PMB-SDCS formulations showed improvement in serum biomarker measurements. Several abnormalities were observed in the kidney, liver, lung, and spleen tissues following PMB treatment, which indicated evidence of toxicity. The docking showed SDCS reduces PMB binding affinity on HSA. The PMB-SDCS formulations were associated with less acute toxicity and less nephrotoxic damage compared with the PMB group. The results were supported by less PMB accumulation in the kidneys in the formulation group. Conclusions: The study indicates that SDCS has the potential to mitigate PMB-induced nephrotoxicity in rat models, suggesting a promising strategy for safer use that warrants further investigation.

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