Drug Delivery System Excellence Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; Molecular Recognition Materials Research Unit, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
Molecular Recognition Materials Research Unit, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
Colloids Surf B Biointerfaces. 2019 Oct 1;182:110374. doi: 10.1016/j.colsurfb.2019.110374. Epub 2019 Jul 17.
This work presents the outcomes of a comparative study of molecular interactions of polymyxin B (PMB) and F12 and F13 formulations in the mole ratios of 1:2 and 1:3 of PMB:sodium deoxycholate sulfate (SDCS), respectively, and a commercial PMB formulation (CPMB) with lipopolysaccharides (LPS). Several spectroscopic and interfacial studies were performed to obtain LPS-peptide interactions at a molecular level. The fluorescence titrimetry method revealed that the F12 formulation (325 nM) exhibited a lower number of binding sites to the LPS compared to CPMB and F13 as well as PMB alone (537 nM). Similarly, in the presence of LPS, the F12 formulation (88 nm) exhibited smaller particle sizes in the dynamic light scattering study compared to PMB (116 nm), CPMB, and the F13 formulation. An interfacial study and circular dichroism spectroscopy revealed PMB and CPMB insertion into the LPS micelles to destabilize and disrupt the LPS membrane, whereas the F12 and F13 formulations may induce pseudo-aggregation. The NMR and IR studies showed that the presence of SDCS, the hydrophobicity of PMB increased by hydrogen bonding and electrostatic interactions and formed stabilized PMB-SDCS micelles. The PMB-SDCS formulation is likely to release PMB for easy penetration into the lipid membrane and cause disruption of the complex LPS micelles. Furthermore, the PMB-SDCS formulations neutralized and detoxified the LPS micelles with minimal toxicity to normal kidney tubular cells as well as an immortalised kidney cell line. The antimicrobial properties of PMBloaded SDCS nanomicelles were effective against a resistant strain of Pseudomonas aeruginosa.
本工作展示了多粘菌素 B (PMB) 与 F12 和 F13 制剂在摩尔比为 1:2 和 1:3 的情况下与去氧胆酸钠硫酸盐 (SDCS) 的分子相互作用的比较研究结果，以及一种商业 PMB 制剂 (CPMB) 与脂多糖 (LPS)。进行了几种光谱和界面研究，以在分子水平上获得 LPS-肽相互作用。荧光滴定法表明，F12 制剂（325 nM）与 CPMB 和 F13 以及单独的 PMB 相比，与 LPS 的结合位点数较少（537 nM）。同样，在 LPS 的存在下，F12 制剂（88 nm）在动态光散射研究中表现出比 PMB（116 nm）、CPMB 和 F13 制剂更小的粒径。界面研究和圆二色性光谱表明，PMB 和 CPMB 插入 LPS 胶束中，使 LPS 膜不稳定并破坏，而 F12 和 F13 制剂可能诱导假性聚集。NMR 和 IR 研究表明，SDCS 的存在增加了 PMB 的疏水性，通过氢键和静电相互作用形成稳定的 PMB-SDCS 胶束。PMB-SDCS 制剂可能会释放 PMB，使其更容易穿透脂质膜，并导致复杂的 LPS 胶束破裂。此外，PMB-SDCS 制剂中和并解毒 LPS 胶束，对正常肾小管细胞和永生化肾细胞系的毒性最小。负载 SDCS 的纳米胶束的 PMB 的抗菌特性对铜绿假单胞菌的耐药株有效。
