Nanocarriers for tuberculosis therapy: Design of safe and effective drug delivery strategies to overcome the therapeutic challenges

Abstract Tuberculosis (TB) is one of the most dreaded infectious diseases associated with a high mortality rate across the globe, especially in developing countries. Mycobacterium tuberculosis (M.tb), the bacteria causing the disease normally affects the lungs and causes pulmonary tuberculosis. However, it can also spread to other areas of the body and can cause secondary tuberculosis. Treatment of TB requires a high dosage of anti-tubercular drugs for a prolonged period. However, the main challenges associated with traditionally used drugs are poor aqueous drug solubility, low penetrability, systemic toxicity at effective doses, off-target accumulation, the mutation in the bacteria leading to multidrug-resistant strains, and lower bactericidal potential of the drug towards the bacteria in macrophages or deep infected tissues. In this context, nanomedicine has been identified to offer distinct advantages that can potentially address the aforementioned challenges. This review outlines the role of nanocarriers in overcoming the challenges associated with; drug solubility and permeation, the effect of reducing bacterial microenvironment on the free drug, and systemic toxicity of chemotherapeutics, etc. The review discusses the application of nanocarriers and their design to regulate the drug release, which ensures its concentration in therapeutic range for an extended duration, improves the efficacy of the drug, decreases the dosing frequency and dose. Also, the targetability of the payload delivery to the site of infection and cell-specific delivery, along with the role of pulmonary nanomedicine in localized and efficient delivery, which consequently reduces the toxicity and therapeutic dose of anti-tubercular drugs against pulmonary tuberculosis has also been discussed systematically.