Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India.
Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India.
Nanomedicine. 2019 Jun;18:402-413. doi: 10.1016/j.nano.2018.11.004. Epub 2018 Nov 16.
We reported earlier about nano-formulation of tetracycline through its entrapment within calcium-phosphate nano-particle (CPNP) and about killing of pathogenic bacterium Shigella flexnari 2a, resistant to tetracycline (and 9 other antibiotics), by the nanonized antibiotic (Tet-CPNP). Here, we report on therapeutic role of Tet-CPNP against deadly diarrheal disease 'shigellosis' in mice, caused by Shigella infection. Our findings revealed that occurrence of mushy-stool excretion, colon-length shortening, weight-loss and bacterial colonization in gastrointestinal tract of mice due to shigellosis was significantly reduced by Tet-CPNP treatment. Histo- and immuno-logical studies showed that changes in morphology and level of inflammatory cytokines TNF-α, IL-1β and IFN-γ in intestinal tissue of Shigella-infected mice were reverted to almost normal features by Tet-CPNP treatment. Bulk tetracycline had no anti-shigellosis action. Thus, nanonization of tetracycline rejuvenated the old, cheap, broad-spectrum antibiotic from obsolescence (due to resistance generation), making it highly beneficial for diarrhea-prone developing countries with limited health-care budgets.
我们之前曾报道过通过将四环素包埋在磷酸钙纳米颗粒（CPNP）中来实现纳米制剂化，以及纳米化抗生素（Tet-CPNP）可以杀死对四环素（和其他 9 种抗生素）耐药的致病性细菌福氏志贺菌 2a。在这里，我们报告了 Tet-CPNP 对由志贺菌感染引起的致命腹泻病“志贺菌病”在小鼠中的治疗作用。我们的研究结果表明，Tet-CPNP 治疗显著减少了由于志贺菌病引起的小鼠软便排泄、结肠缩短、体重减轻和胃肠道细菌定植的发生。组织学和免疫组织化学研究表明，Tet-CPNP 治疗使感染志贺菌的小鼠肠道组织中形态和炎症细胞因子 TNF-α、IL-1β 和 IFN-γ 的水平发生的变化几乎恢复到正常特征。大剂量四环素没有抗志贺菌作用。因此，纳米化四环素使这种古老的、廉价的、广谱抗生素摆脱了因耐药性而被淘汰的命运（由于耐药性的产生），这对预算有限的发展中国家非常有益，这些国家容易发生腹泻。
