Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara, Italy.
Biofilms-Research Center for Biointerfaces, Faculty of Health and Society, Malmö University, SE-20506 Malmö, Sweden.
Molecules. 2020 Nov 30;25(23):5655. doi: 10.3390/molecules25235655.
Biofilm production is regulated by the Quorum Sensing system. Nowadays, Quorum Sensing represents an appealing target to design new compounds to increase antibiotics effects and avoid development of antibiotics multiresistance. In this research the use of liposomes to target two novel synthetic biofilm inhibitors is presented, focusing on a preformulation study to select a liposome composition for in vitro test. Five different liposome (LP) formulations, composed of phosphatidyl choline, cholesterol and charged surfactant (2:1:1, molar ratio) have been prepared by direct hydration and extrusion. As charged surfactants dicetyl phosphate didecyldimethylammonium chloride, di isobutyl phenoxy ethyl dimethyl benzyl ammonium chloride and stearylamine (SA) and have been used. Liposome charge, size and morphology were investigated by zeta potential, photon correlation spectroscopy, small angle x-ray spectroscopy and electron microscopy. LP-SA was selected for the loading of biofilm inhibitors and subjected to high performance liquid chromatography for entrapment capacity evaluation. LP-SA loaded inhibitors showed a higher diameter (223.6 nm) as compared to unloaded ones (205.7 nm) and a dose-dependent anti-biofilm effect mainly after 48 h of treatment, while free biofilm inhibitors loose activity. In conclusion, our data supported the use of liposomes as a strategy to enhance biofilm inhibitors effect.
生物膜的产生受群体感应系统调控。目前，群体感应已成为设计新化合物的一个有吸引力的靶点，以增加抗生素的效果并避免抗生素耐药性的产生。在这项研究中，我们使用脂质体来靶向两种新型合成生物膜抑制剂，重点是进行预配方研究，以选择用于体外测试的脂质体组成。通过直接水合和挤压制备了五种不同的脂质体（LP）配方，由磷脂酰胆碱、胆固醇和带电荷的表面活性剂（2:1:1，摩尔比）组成。使用了带电荷的表面活性剂二乙酰基磷酸二癸基二甲基氯化铵、二异丁基苯氧基乙基二甲基苄基氯化铵和硬脂胺（SA）。通过 zeta 电位、光子相关光谱、小角 X 射线光谱和电子显微镜研究了脂质体的电荷、大小和形态。选择 LP-SA 来负载生物膜抑制剂，并通过高效液相色谱法评估包封率。与未负载的抑制剂相比，负载抑制剂的 LP-SA 显示出更高的直径（223.6nm）和剂量依赖性的抗生物膜作用，主要在治疗 48 小时后，而游离的生物膜抑制剂则失去活性。总之，我们的数据支持使用脂质体作为增强生物膜抑制剂效果的策略。
