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Sulfonium-based liposome-encapsulated antibiotics deliver a synergistic antibacterial activity
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2021-5-24 , DOI: 10.1039/d1md00091h
Anjali Patel 1 , Subhasis Dey 2 , Kamal Shokeen 3 , Tomasz M Karpiński 4 , Senthilkumar Sivaprakasam 3 , Sachin Kumar 3 , Debasis Manna 1, 2
Affiliation  

The devastating antibacterial infections, coupled with their antibiotic resistance abilities, emphasize the need for effective antibacterial therapeutics. In this prospect, liposomal delivery systems have been employed in improving the efficacy of the antibacterial agents. The liposome-based antibiotics enhance the therapeutic potential of the new or existing antibiotics and reduce their adverse effects. The current study describes the development of sulfonium-based antibacterial lipids that demonstrate the delivery of existing antibiotics. The presence of cationic sulfonium moieties and inherent membrane targeting abilities of the lipids could help reduce the antibiotic resistance abilities of the bacteria and deliver the antibiotics to remove the infectious pathogens electively. The transmission electron microscopic images and dynamic light scattering analyses revealed the liposome formation abilities of the sulfonium-based amphiphilic compounds in the aqueous medium. The effectiveness of the compounds was tested against the Gram-negative and Gram-positive bacterial strains. The viability of the bacterial cells was remarkably reduced in the presence of the compounds. The sulfonium-based compounds with pyridinium moiety and long hydrocarbon chains showed the most potent antibacterial activities among the tested compounds. Mechanistic studies revealed the membrane-targeted bactericidal activities of the compounds. The potent compound also showed tetracycline and amoxicillin encapsulation and sustained release profiles in the physiologically relevant medium. The tetracycline and amoxicillin-encapsulated lipid showed much higher antibacterial activities than the free antibiotics at similar concentrations, emphasizing the usefulness of the synergistic effect of sulfonium-based lipid and the antibiotics, signifying that the sulfonium lipid penetrated the bacterial membrane and increased the cellular uptake of the antibiotics. The potent lipid also showed therapeutic potential, as it is less toxic to mammalian cells (like HeLa and HaCaT cells) at concentrations higher than their minimum inhibitory concentration values against S. aureus, E. coli, and MRSA. Hence, the sulfonium-based lipid exemplifies a promising framework for assimilating various warheads, and provides a potent antibacterial material.

中文翻译:

锍基脂质体封装抗生素具有协同抗菌活性

毁灭性的抗菌感染,加上它们的抗生素耐药性,强调了有效抗菌治疗的必要性。在这个前景中,脂质体递送系统已被用来提高抗菌剂的功效。基于脂质体的抗生素增强了新的或现有抗生素的治疗潜力并减少了它们的副作用。目前的研究描述了基于锍的抗菌脂质的开发,该脂质证明了现有抗生素的输送。阳离子锍部分的存在和脂质固有的膜靶向能力可以帮助降低细菌的抗生素耐药性并递送抗生素以选择性地去除传染性病原体。透射电子显微镜图像和动态光散射分析揭示了锍基两亲化合物在水介质中的脂质体形成能力。测试了这些化合物针对革兰氏阴性和革兰氏阳性细菌菌株的有效性。在这些化合物的存在下,细菌细胞的活力显着降低。在测试的化合物中,具有吡啶部分和长烃链的锍基化合物显示出最有效的抗菌活性。机理研究揭示了这些化合物的膜靶向杀菌活性。这种有效的化合物还显示出四环素和阿莫西林的封装以及在生理相关介质中的持续释放曲线。在相似浓度下,四环素和阿莫西林包封的脂质比游离抗生素表现出更高的抗菌活性,强调了锍基脂质和抗生素的协同作用,表明锍脂质穿透细菌膜并增加细胞摄取抗生素。这种有效的脂质还显示出治疗潜力,因为当其浓度高于对金黄色葡萄球菌大肠杆菌和 MRSA 的最低抑制浓度值时,它对哺乳动物细胞(如 HeLa 和 HaCaT 细胞)的毒性较小。因此,锍基脂质是同化各种弹头的有前景的框架的典范,并提供了有效的抗菌材料。
更新日期:2021-05-24
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