Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: Therapeutic assessment in a murine model of tuberculosis infection.,European Journal of Pharmaceutics and Biopharmaceutics

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Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: Therapeutic assessment in a murine model of tuberculosis infection.
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.4 ) Pub Date : 2019-11-30 , DOI: 10.1016/j.ejpb.2019.11.009
Ana Grenha ₁ , Ana D Alves ₁ , Filipa Guerreiro ₁ , Jacinta Pinho ₂ , Sandra Simões ₂ , António José Almeida ₂ , Maria Manuela Gaspar ₂

Affiliation

Tuberculosis is a leading cause of death worldwide. Although the development of new antimycobacterial drugs is an obvious and necessary strategy to address the disease, improving the therapeutic performance of drugs already approved constitutes a valuable alternative approach. As the lung is the most affected organ, where M. tuberculosis is able to survive and proliferate, the direct pulmonary delivery of antitubercular drugs comprises a highly promising therapeutic strategy. In this work, spray-dried locust bean gum (LBG) microparticles were used to deliver a combination of two first line antitubercular drugs, isoniazid (INH) and rifabutin (RFB), to the alveolar zone, where macrophages hosting the bacteria reside. LBG is expected to mediate favoured macrophage uptake of microparticles, leading to enhanced therapeutic effect. The therapeutic effect of LBG/INH/RFB microparticles was evaluated in a murine model infected with M. tuberculosis, strain H37Rv and compared with oral co-therapy of INH and RFB in the free form. The pulmonary administration of LBG/INH/RFB microparticles 5 times per week was the only treatment schedule that provided negative growth index values in lung (-0.22), spleen (-0.14) and liver (-0.26) even using a lower therapeutic dose for both antibiotics. For the control group, the respective values were +1.95, +0.75 and +0.96.

中文翻译：

联合使用异烟肼和利福布丁的可吸入刺槐豆胶微粒：在结核病感染鼠模型中的治疗评估。

结核病是世界范围内主要的死亡原因。尽管开发新的抗分枝杆菌药物是解决该疾病的明显且必要的策略，但是改善已获批准的药物的治疗性能是一种有价值的替代方法。由于肺是受影响最严重的器官，结核分枝杆菌能够在其中存活和增殖，因此抗结核药物的直接肺部输送是一种很有前途的治疗策略。在这项工作中，使用喷雾干燥的刺槐豆胶（LBG）微粒将两种一线抗结核药物异烟肼（INH）和利福布汀（RFB）的组合递送至肺泡区，在肺泡区托管了细菌的巨噬细胞。LBG有望介导微粒对巨噬细胞的有利摄取，从而提高治疗效果。在感染了结核分枝杆菌，H37Rv株的鼠模型中评估了LBG / INH / RFB微粒的治疗效果，并与游离形式的INH和RFB口服联合治疗进行了比较。每周对肺LBG / INH / RFB微粒进行5次肺部给药是唯一的治疗方案，即使使用较低的治疗剂量，其肺（-0.22），脾（-0.14）和肝（-0.26）的生长指数均呈负值。两种抗生素。对于对照组，各自的值为+ 1.95，+ 0.75和+0.96。每周对肺LBG / INH / RFB微粒进行5次肺部给药是唯一的治疗方案，即使使用较低的治疗剂量，其肺（-0.22），脾（-0.14）和肝（-0.26）的生长指数均呈负值。两种抗生素。对于对照组，各自的值为+ 1.95，+ 0.75和+0.96。每周对肺LBG / INH / RFB微粒进行5次肺部给药是唯一的治疗方案，即使使用较低的治疗剂量，其肺（-0.22），脾（-0.14）和肝（-0.26）的生长指数均呈负值。两种抗生素。对于对照组，各自的值为+ 1.95，+ 0.75和+0.96。

更新日期：2019-11-30

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