Bartomeu Garcia Caterina, Shi Di, Webster Thomas J
Department of Chemical Engineering, Universitat Rovira i Virgili, Tarragona, Spain.
Department of Chemical Engineering, Northeastern University, Boston, MA, USA.
Int J Nanomedicine. 2017 Apr 12;12:3009-3021. doi: 10.2147/IJN.S130125. eCollection 2017.
Bacterial meningitis has become a global concern, because of the emergence of antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter bacteria, thus providing a possible treatment for numerous infections, including meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse with the bacteria membrane and promote intracellular drug release. Moreover, this ability can be improved by using cell-penetrating peptides (such as Tat47-57, which is a peptide derived from the Tat protein of HIV). The purpose of this in vitro study was to demonstrate for the first time the ability of the presently prepared fusogenic liposomes, which were spherical particles with a diameter of 100 nm loaded with antibiotics and functionalized with-cell penetrating peptides (Tat), to fight the main bacteria that cause meningitis. For this, vancomycin, methicillin, and ampicillin antibiotics were loaded inside fusogenic liposomes to fight , methicillin-resistant , and . Antibacterial activity of Tat-functionalized and nonfunctionalized liposomes loaded with antibiotics was tested by determining bacteria colony-forming units and growth-curve assays coupled with live/dead assays using fluorescence microscopy. Results showed a remarkable decrease in antibiotic minimum inhibitory concentration when all of the bacteria were treated with these novel liposomes, especially for the functionalized liposomes loaded with methicillin. With antibiotic concentrations of 1.7-3 µg/mL for Tat-functionalized liposomes loaded with methicillin, the bacteria population was totally eradicated. Cytotoxicity tests with astrocytes and endothelial cells, major cellular components of the blood-brain barrier, were also performed for all of the liposomes, including free antibiotic and the Tat peptide. Results showed much promise for the further study of the presently formulated liposomes to treat meningitis.
由于抗生素耐药菌的出现，细菌性脑膜炎已成为一个全球关注的问题。已经证明脂质体可以进入细菌，从而为包括脑膜炎在内的多种感染提供了一种可能的治疗方法。融合脂质体对pH敏感，具有与细菌膜融合并促进细胞内药物释放的高能力。此外，通过使用细胞穿透肽（如Tat47 - 57，它是一种源自HIV的Tat蛋白的肽）可以提高这种能力。这项体外研究的目的是首次证明目前制备的融合脂质体（其为直径100 nm的球形颗粒，负载抗生素并用细胞穿透肽（Tat）功能化）对抗引起脑膜炎的主要细菌的能力。为此，将万古霉素、甲氧西林和氨苄青霉素抗生素负载到融合脂质体中，以对抗耐甲氧西林金黄色葡萄球菌和肺炎链球菌。通过测定细菌集落形成单位以及结合使用荧光显微镜的活/死检测的生长曲线分析，测试了负载抗生素的Tat功能化和非功能化脂质体的抗菌活性。结果表明，当用这些新型脂质体处理所有细菌时，抗生素最低抑菌浓度显著降低，尤其是对于负载甲氧西林的功能化脂质体。对于负载甲氧西林的Tat功能化脂质体，抗生素浓度为1.7 - 3 µg/mL时，细菌群体被完全根除。还对所有脂质体，包括游离抗生素和Tat肽，进行了对星形胶质细胞和内皮细胞（血脑屏障的主要细胞成分）的细胞毒性测试。结果表明，目前配制的脂质体在治疗脑膜炎的进一步研究方面很有前景。
