Abstract
AbstractThe appearance and rapid spread of drug resistant strains of tuberculosis (TB), one of the deadliest infectious diseases, pose a serious threat to public health and increase the need for shorter, less toxic, and more effective therapies. Developing new drugs is difficult and often associated with side effects, so nanotechnology has emerged as a tool to improve current treatments and to rescue drugs having elevated toxicity or poor solubility. Due to their size and surface chemistry, antimicrobial‐loaded nanocarriers are avidly taken up by macrophages, the main cells hosting Mycobacterium tuberculosis. Macrophages are continuously recruited to infected areas, they can transport drugs with them, making passive targeting a good strategy for TB treatment. Active targeting (decorating surface of nanocarriers with ligands specific to receptors displayed by macrophages) further increases local drug concentration, and thus treatment efficacy. Although in in vivo studies, nanocarriers are often administered intravenously in order to avoid inaccurate dosage in animals, translation to humans requires more convenient routes like pulmonary or oral administration. This report highlights the importance and progress of pulmonary administration, passive and active targeting strategies toward bacteria reservoirs to overcome the challenges in TB treatment.
Highlights
(TB), one of the deadliest infectious diseases, pose a serious threat to public ficiency virus infection and acquired imhealth and increase the need for shorter, less toxic, and more effective therapies
Upon entry into the lungs, Mycobacterium tuberculosis (Mtb) is engulfed by AMs, which are the dominant cell type that the pathogen infects; other cell types that can be infected by Mtb are interstitial macrophages and dendritic cells
A situation similar to latent TB infection (LTBI) may occur after a drug-based treatment of active disease, when the bacteria are not fully eliminated and those few that are still present in the body can be maintained in a latent condition that may result in relapse after a period of time.[1,27]
Summary
(RIF), pyrazinamide (PZA), and ethambutol (ETB), followed by a 4-month continuation phase of INH plus RIF.[3,4] Treatment. The bacilli are exposed to a variety of stressful conditions, such as hypoxia, acidic pH, low iron availability, and nutrient deprivation.[24] In order to overcome these challenging host immune responses, the bacteria have evolved mechanisms to maintain viability with limited or no replication This state (called dormancy) is characterized by low metabolic activity and a change in the composition and spatial architecture of the cell wall[25] and bacteria show phenotypic drug tolerance to antibiotics targeting functions required for growth.[26] granulomas establish a dynamic balance between host defenses and bacterial dormancy. The collapse of the granuloma releases the bacteria to blood capillaries and the alveolar space and disseminates to other parts of the lung and to other organs ( producing extrapulmonary tuberculosis), in order to fully develop an active disease (meaning that they present clinical symptoms) and to be transmitted to other individuals.[1,17,18,19,29]
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