Abstract
Tuberculosis (TB) is caused by a bacterial infection that affects a number of human organs, primarily the lungs, but also the liver, spleen, and spine, causing key symptoms of fever, fatigue, and persistent cough, and if not treated properly, can be fatal. Every year, 10 million individuals become ill with active TB resulting with a mortality approximating 1.5 million. Current treatment guidelines recommend oral administration of a combination of first-line anti-TB drugs for at least 6 months. While efficacious under optimum conditions, ‘Directly Observed Therapy Short-course’ (DOTS) is not without problems. The long treatment time and poor pharmacokinetics, alongside drug side effects lead to poor patient compliance and has accelerated the emergence of multi-drug resistant (MDR) organisms. All this, combined with the limited number of newly discovered TB drugs to treat MDR-TB and shorten standard therapy time, has highlighted the need for new targeted drug delivery systems. In this respect, there has been recent focus on micro- and nano-particle technologies to prepare organic or/and metal particles loaded with TB drugs to enhance their efficacy by targeted delivery via the inhaled route. In this review, we provide a brief overview of the current epidemiology of TB, and risk factors for progression of latent stage tuberculosis (LTBI) to the active TB. We identify current TB treatment regimens, newly discovered TB drugs, and identify studies that have used micro- or nano-particles technologies to design a reliable inhalation drug delivery system to treat TB more effectively.
Highlights
TB, an airborne infectious disease caused by Mycobacterium tuberculosis (M.tb), is a major public health issue associated with a high rate of morbidity and mortality [1]
Antimicrobial treatment is available but takes too long and has side effects leading to poor patient compliance and the emergence of drug resistant organisms
Micro- and nano-particle technologies are sufficiently mature for use in robust inhalation drug delivery systems to deliver antimicrobial therapy more effectively to the major site of Tuberculosis in the lung
Summary
TB, an airborne infectious disease caused by Mycobacterium tuberculosis (M.tb), is a major public health issue associated with a high rate of morbidity and mortality [1]. The resistance of M.tb to the antitubercular drugs along with a lack of new drugs for the treatment of bacterial infections suggest the need to utilize novel antibacterial agents In this respect, metal nanoparticles such as silver and zinc have been studied extensively as a potential treatment for many medical conditions [44]. Studies have reported the antimicrobial effect of AgNPs on resistant strains of bacteria through several mechanisms [49] These include disturbance of bacterial membranes and cell walls leading to cell leakage by increasing membrane permeability [50], initiating lipid peroxidation and reduction in the levels of the antioxidant, glutathione, depolarization of mitochondria, and oxidative damage of DNA with apoptotic cell death [51], damaging of bacterial cell DNA by binding to its sulfur and phosphorus groups [52], and by releasing Ag ions which play an important antibacterial role by interacting with bacterial cell membranes [53]. Employing gold NPs in the detection of TB DNA for diagnostic purposes, using a paper-based analytical platform, resulted in a highly sensitive detection limit of 1.95 × 10–2 ng/ml for TB DNA [61]
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