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Effect of sodium deoxycholate sulfate on outer membrane permeability and neutralization of bacterial lipopolysaccharides by polymyxin B formulations
Ist Teil von
International journal of pharmaceutics, 2020-05, Vol.581, p.119265, Article 119265
Ort / Verlag
Netherlands: Elsevier B.V
Erscheinungsjahr
2020
Link zum Volltext
Quelle
Elsevier ScienceDirect Journals Complete
Beschreibungen/Notizen
[Display omitted]
We demonstrated binding interactions of polymyxin B (PMB), PMB formulations in the mole ratios of 1:2 and 1:3 of PMB:sodium deoxycholate sulfate (SDCS) and a commercial PMB formulation (CPMB) with lipopolysaccharides (LPS). The 1:2 PMB formulation (78.5–135.2 nM) exhibited a lower number of binding sites to the tested LPS compared to CPMB (112.6–140.9 nM) whereas 1:3 PMB formulation exhibited a higher number of binding sites (143.9–340.2 nM). Similarly, in the presence of LPS, the 1:2 PMB formulation (163.8–221.4 nm) exhibited smaller particle sizes compared to PMB, CPMB and 1:3 PMB formulation (248.8–603.5 nm). Molecular docking simulation suggested that the fatty acyl tails of LPS wrap together to produce a pseudo-globular structure of PMB-LPS complex, and among those 1:2 PMB formulation formed a more stable structure. The primary forces behind this complex are hydrogen bonds and salt bridges among the LPS, PMB, and SDCS. This study revealed that the PMB, CPMB, and PMB formulations inserted into the LPS micelles to disrupt the LPS membrane, whereas the SDCS may induce aggregation. The 1:2 PMB formulation also had higher bacterial uptake than other PMB formulations. The 1:2 PMB formulation neutralized the LPS micelles and was effective against Escherichia coli and Pseudomonas aeruginosa.