Mycobacteria Research Laboratory, Department of Biological Sciences, Institute of Structural and Molecular Biology (ISMB), Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
Material Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia.
Molecules. 2017 Oct 12;22(10):1560. doi: 10.3390/molecules22101560.
Tuberculosis (TB) is a bacterial disease responsible for millions of infections and preventable deaths each year. Its treatment is complicated by patients' noncompliance due to dosing frequency, lengthy treatment, and adverse side effects associated with current chemotherapy. However, no modifications to the half-a-century old standard chemotherapy have been made based on a nanoformulation strategy to improve pharmacokinetic efficacy. In this study, we have designed a new nanodelivery formulation, using graphene oxide as the nanocarrier, loaded with the anti-TB antibiotic, ethambutol. The designed formulation was characterized using a number of molecular analytical techniques. It was found that sustained release of the drug resulted in better bioavailability. In addition, the designed formulation demonstrated high biocompatibility with mouse fibroblast cells. The anti-TB activity of the nanodelivery formulation was determined using whole-cell resazurin microtiter plate assay, modified-spot culture growth inhibition assay, and biofilm inhibition assay. The nanodelivery formulation showed good anti-mycobacterial activity. The anti-mycobacterial activity of Ethambutol was unaffected by the drug loading and release process. The results of this study demonstrated the potential of this new nanodelivery formulation strategy to be considered for modifying existing chemotherapy to yield more efficacious antibiotic treatment against TB.
结核病（TB）是一种细菌病，每年导致数百万人感染和可预防的死亡。由于剂量频率、治疗时间长以及与当前化疗相关的不良反应，患者不遵医嘱的情况使治疗变得复杂。然而，基于纳米制剂策略来改善药代动力学疗效，并没有对半个世纪以来的标准化疗进行任何修改。在这项研究中，我们设计了一种新的纳米递药制剂，使用氧化石墨烯作为纳米载体，负载抗结核抗生素乙胺丁醇。该设计的制剂使用多种分子分析技术进行了表征。结果发现，药物的持续释放导致更好的生物利用度。此外，该设计的制剂表现出与小鼠成纤维细胞的高生物相容性。使用全细胞 Resazurin 微量板测定法、改良斑点培养生长抑制测定法和生物膜抑制测定法确定纳米递药制剂的抗结核活性。纳米递药制剂显示出良好的抗分枝杆菌活性。乙胺丁醇的抗分枝杆菌活性不受药物负载和释放过程的影响。这项研究的结果表明，这种新的纳米递药制剂策略具有潜力，可用于修改现有的化疗方案，以产生更有效的抗结核抗生素治疗。
