Amrita Center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham University, AIMS-Ponekkara, Cochin, PIN: 682041, India.
Curr Drug Deliv. 2014;11(6):744-52. doi: 10.2174/1567201811666140619121728.
Antimicrobial therapy of infections caused by M. tuberculosis is a challenge due to poor response to therapy and recurrent infections. Under in vitro conditions, antibiotics effectively kill M. tuberculosis within the first two weeks. However, an extended treatment time of 6-9 months is required to eradicate M. tuberculosis infection, mainly due to the intracellular survival of this pathogen and poor penetration of the antibiotics into the intracellular compartment of the host cells. Recent advances in the field of drug delivery have led to the use of different antibiotic incorporated nano- and micro- formulations such as liposomes, polymeric particles, mesoporous silica particles and particulate suspensions for targeted drug delivery applications into the intracellular compartment of the macrophages. The drug incorporated nano- and micro-particles are prone to be easily internalized, which leads to preferential delivery of the drugs into the tissues and organs of interest. Other advantages of these nano- and micro-particles over the free drugs are their comparatively higher stability and bioavailability. This review highlights the current strategies and challenges in treatment, the different antibiotics available, their modes of action, generation and mechanism of drug resistance and recent advances in the intracellular drug delivery using nanoparticles for the treatment of tuberculosis.
由于治疗反应差和反复感染,分枝杆菌感染的抗菌治疗是一个挑战。在体外条件下,抗生素能在最初的两周内有效杀灭结核分枝杆菌。然而,需要 6-9 个月的延长治疗时间来根除结核分枝杆菌感染,主要是由于该病原体在细胞内的存活和抗生素对宿主细胞内室的穿透不良。药物传递领域的最新进展导致使用不同的抗生素包封纳米和微制剂,如脂质体、聚合物颗粒、介孔硅颗粒和颗粒悬浮液,用于将药物靶向递送至巨噬细胞的细胞内室。包含抗生素的纳米和微颗粒易于被内化,从而优先将药物递送至感兴趣的组织和器官。与游离药物相比,这些纳米和微颗粒的其他优点是它们具有较高的稳定性和生物利用度。本文综述了治疗方面的当前策略和挑战、现有的不同抗生素、它们的作用模式、耐药性的产生和机制,以及使用纳米颗粒进行细胞内药物递送来治疗结核病的最新进展。