Novel formulation of antimicrobial peptides enhances antimicrobial activity against methicillin-resistantStaphylococcus aureus(MRSA)
Novel formulation of antimicrobial peptides enhances antimicrobial activity against methicillin-resistantStaphylococcus aureus(MRSA)
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DOI：
10.1007/s00726-020-02903-7
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发表时间：
2020-10-19
期刊：
影响因子：
3.5
通讯作者：
Govender, Thirumala
中科院分区：
文献类型：
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作者：
Faya, Mbuso;Hazzah, Heba A.;Govender, Thirumala
抗菌肽（AMPs）具有穿透和运输细菌细胞膜的能力，并且它们已被标记为具有药物传递功能的特殊候选者。本研究的目的是研究新型抗菌肽制剂对增强MRSA活性的有效性。采用薄膜水合法制备脂质体，其中含有磷脂酰胆碱、胆固醇、油酸、新型AMP和万古霉素（VCM）。抗菌肽和脂质体的表征包括HPLC和LCMS，用于肽的纯度和质量测定；DLS（尺寸、多分散性、zeta电位）、TEM（表面形貌）、透析（药物释放）、肉汤稀释和流式细胞术（抗菌活性）；MTT测定，溶血和细胞内抗菌研究。载药AMP(2)- lipo1的尺寸、PDI和zeta电位分别为102.6 +/- 1.81 nm、0.157 +/- 0.01和- 9.81 +/- 1.69 mV；载药AMP(3)- lipo2的尺寸、PDI和zeta电位在pH 7.4下分别为146.4 +/- 1.90 nm、0.412 +/- 0.05和- 4.27 +/- 1.25 mV。然而，在两种配方的酸性pH下，我们观察到尺寸，PDI和正向zeta电位的转换增加，这表明我们的脂质体系统的pH响应性。体外药物释放研究表明，脂质体制剂在pH 6.0时释放VCM-HCl的速度比pH 7.4更快。体外抑菌活性研究。金黄色葡萄球菌和MRSA显示，脂质体在pH值为6时比pH值为7.4时活性增强。研究表明，该制剂可以潜在地用于增强抗菌肽的活性和渗透，从而改善细菌感染的治疗。
Antimicrobial peptides (AMPs) have the ability to penetrate as well as transport cargo across bacterial cell membranes, and they have been labeled as exceptional candidates to function in drug delivery. The aim of this study was to investigate the effectiveness of novel formulation of AMPs for enhanced MRSA activity. The strategy was carried out through the formulation of liposomes by thin-layer film hydration methodology, containing phosphatidylcholine, cholesterol, oleic acid, the novel AMP, as well as vancomycin (VCM). Characterization of the AMPs and liposomes included HPLC and LCMS for peptide purity and mass determination; DLS (size, polydispersity, zeta potential), TEM (surface morphology), dialysis (drug release), broth dilution, and flow cytometry (antibacterial activity); MTT assay, haemolysis and intracellular antibacterial studies. The size, PDI, and zeta potential of the drug-loaded AMP(2)-Lipo-1 were 102.6 +/- 1.81 nm, 0.157 +/- 0.01, and - 9.81 +/- 1.69 mV, respectively, while for AMP(3)-Lipo-2 drug-loaded formulation, it was 146.4 +/- 1.90 nm, 0.412 +/- 0.05, and - 4.27 +/- 1.25 mV respectively at pH 7.4. However, in acidic pH for both formulations, we observed an increase in size, PDI, and a switch to positive zeta potential, which indicated the pH responsiveness of our liposomal systems. The in vitro drug release studies demonstrated that liposomal formulations released VCM-HCl at a faster rate at pH 6.0 compared to pH 7.4. In vitro antibacterial activity againstS. aureusand MRSA revealed that liposomes had enhanced activity at pH 6 compared to pH 7.4. The study revealed that the formulation can potentially be used to enhance activity and penetration of AMPs, thereby improving the treatment of bacterial infections.