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|Title:||Potential of sodium deoxycholate sulfate as a carrier for polymyxin B: Physicochemical properties, bioactivity and in vitro safety|
University of Karachi
Faculty of Medicine, Siriraj Hospital, Mahidol University
Prince of Songkla University
|Keywords:||Pharmacology, Toxicology and Pharmaceutics|
|Citation:||Journal of Drug Delivery Science and Technology. Vol.58, (2020)|
|Abstract:||© 2020 Elsevier B.V. Polymyxin B (PMB) is used as the last line therapy for multidrug-resistant Gram-negative bacterial infections; however, nephrotoxicity is still a concern. Here, PMB carried with sodium deoxycholate sulfate (SDCS) was developed, which aimed to improve the safety profile while preserving the antimicrobial activity. PMB micelles showed excellent stability after reconstitution in aqueous solutions. The mean particle sizes of the formulations were in the nano levels, which did not change after reconstitution and storage for 48 h at room temperature, which was confirmed by images from confocal laser scanning microscopy. The PMB micelles exhibited a more negative charge than the PMB prototype. FT-IR, 1H-NMR spectroscopy, and molecular docking revealed that SDCS interacted with PMB via H-bonding without affecting the PMB structure. Furthermore, the PMB micelles showed that SDCS promoted a sustained release profile under simulated physiological conditions, which reduced the hemolytic effect and toxicity to kidney cells while the MICs against carbapenem-resistant Acinetobacter baumannii were 0.5–2 μg/ml. These findings could provide the crucial evidence of PMB micelles and give insight into the proposed mechanisms of these complexes leading to less toxicity resulting in implications for safety and effectiveness in bacterial infection treatment.|
|Appears in Collections:||Scopus 2020|
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