Nanoweapons Against Tuberculosis

Abstract

The emerging resistance of Mycobacterium tuberculosis and other so-called nontuberculous mycobacteria to clinically used drugs, including second- and third-choice drugs, and the development of cross-resistant or multidrug-resistant strains are alarming. An increase in the number of these infections and the occurrence of nontuberculous opportunistic species are caused by the general immunosuppression of patients, and this fact makes these diseases extremely serious. In spite of the mentioned, the discovery and development of new drugs for systemic administration has not been a priority, as it is a relatively long and risky procedure. Thus, the preparation of nanoparticles/nanoformulations of clinically used drugs can be an approach of first choice. In general, nanomaterials represent a noteworthy alternative for treatment and mitigation of infections caused by resistant pathogens, which are unlikely to develop resistance to nanomaterials. In contrast to conventional drugs, nanomaterials exert efficiency through various mechanisms; in addition to the drug activity itself, they show “intrinsic effects, " such as damaging the membrane morphology, disruption of transmembrane energy metabolism and the membrane electron transport chain, generation of reactive oxygen species, etc. In addition, the application of nanoformulations enhances the bioavailability of active substances and enables targeted delivery and controlled release. This contribution provides an exhaustive overview of the investigated nano-based formulations of antimycobacterially effective drugs, such as isoniazid, ethambutol, rifampicin, and bedaquiline. These nanoformulations increase biological potency, as they can ensure fixed-dose drug combinations or nanoencapsulation of drugs with biologically active matrices. In addition, the route of administration can be modified; thus, nano-based drug delivery systems demonstrate significant potential reducing the dosing frequency and shortening the time of treatment. Brief attention is also given to new nanoformulated antituberculosis vaccines. Future prospects of the application of nanotechnology in the treatment of tuberculosis are briefly outlined.