Nanotechnology-based targeted drug delivery: An emerging tool to overcome tuberculosis

The 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.This work was supported by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement No. 842652, the Spanish MICINN projects (Grant Nos. BIO2017-84246-C2-1-R, SAF2017-84839-C2-1-R, and CTQ2015-66869-P), and by the Gobierno de Aragón (Diputación General de Aragón–Fondo Social Europeo). R.M.-R. acknowledges MICINN for funding through the Ramón y Cajal Program (Grant No. RYC-2013-12570). H.S.-C. and A.C.M.-P. are grateful for FPU predoctoral contracts from Ministerio de Educación Cultura y Deporte (Spain) and M.A. is grateful for a predoctoral contract from Gobierno de Aragón (Diputación General de Aragón–Fondo Social Europeo).Peer reviewe