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由巨噬细胞系膜脂质提取物组成的脂质体作为锥虫杀剂 '- 方酸酰胺 17 向……的递送载体

Liposomes Composed by Membrane Lipid Extracts from Macrophage Cell Line as a Delivery of the Trypanocidal ,'-Squaramide 17 towards .

作者信息

Quijia Christian Rafael, Bonatto Cínthia Caetano, Silva Luciano Paulino, Andrade Milene Aparecida, Azevedo Clenia Santos, Lasse Silva Camila, Vega Manel, de Santana Jaime Martins, Bastos Izabela Marques Dourado, Carneiro Marcella Lemos Brettas

机构信息

Microscopy Laboratory, Department of Cell Biology, Institute of Biology, University of Brasília, UnB-Brasilia, Federal District, Brasília DF 70910-900, Brazil.

Laboratory of Nanobiotechnology, Embrapa Genetic Resources and Biotechnology, Parque Estação Biológica, PqEB, Av. W5 Norte (Final) Caixa Postal 02372, Brasília DF 70.770-917, Brazil.

出版信息

Materials (Basel). 2020 Dec 2;13(23):5505. doi: 10.3390/ma13235505.

Abstract

Chagas is a neglected tropical disease caused by , and affects about 25 million people worldwide. , '-Squaramide 17 (S) is a trypanocidal compound with relevant in vivo effectiveness. Here, we produced, characterized, and evaluated cytotoxic and trypanocidal effects of macrophage-mimetic liposomes from lipids extracted of RAW 264.7 cells to release S. As results, the average hydrodynamic diameter and Zeta potential of mimetic lipid membranes containing S (MLS) was 196.5 ± 11 nm and -61.43 ± 2.3 mV, respectively. Drug entrapment efficiency was 73.35% ± 2.05%. After a 72 h treatment, MLS was observed to be active against epimastigotes in vitro (IC = 15.85 ± 4.82 μM) and intracellular amastigotes (IC = 24.92 ± 4.80 μM). Also, it induced low cytotoxicity with CC of 1199.50 ± 1.22 μM towards VERO cells and of 1973.97 ± 5.98 μM in RAW 264.7. MLS also induced fissures in parasite membrane with a diameter of approximately 200 nm in epimastigotes. MLS showed low cytotoxicity in mammalian cells and high trypanocidal activity revealing this nanostructure a promising candidate for the development of Chagas disease treatment.

摘要

恰加斯病是一种由……引起的被忽视的热带疾病,全球约有2500万人受其影响。……“-Squaramide 17 (S)是一种具有相关体内有效性的杀锥虫化合物。在此,我们制备、表征并评估了从RAW 264.7细胞提取的脂质制成的模拟巨噬细胞脂质体释放S的细胞毒性和杀锥虫作用。结果显示,含S的模拟脂质膜(MLS)的平均流体动力学直径和Zeta电位分别为196.5±11 nm和-61.43±2.3 mV。药物包封效率为73.35%±2.05%。经过72小时的处理,观察到MLS在体外对无鞭毛体具有活性(IC = 15.85±4.82 μM),对细胞内无鞭毛体也有活性(IC = 24.92±4.80 μM)。此外,它对VERO细胞的CC为1199.50±1.22 μM,对RAW 264.7细胞的CC为1973.97±5.98 μM,诱导的细胞毒性较低。MLS还在无鞭毛体的寄生虫膜上诱导出直径约为200 nm的裂缝。MLS在哺乳动物细胞中显示出低细胞毒性和高杀锥虫活性,表明这种纳米结构是恰加斯病治疗开发的一个有前景的候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c628/7730638/12daf70b864a/materials-13-05505-g001.jpg

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