Isoniazid Nano-drug Delivery Systems Targeting Macrophages for the Treatment of Tuberculosis

Abstract

In the current clinical setting, the management of Mycobacterium tuberculosis remains a challenge. Isoniazid (INH) remains a drug of choice for treating tuberculosis (TB) via the conventional oral route. However, INH has low plasma levels due to its poor permeability into the bacterial cell. Furthermore, it has a short half-life of 1–4 h, indicating a brief residence in the plasma. Therefore, multiple administration frequencies at high doses are required, leading to multi-drug resistance and other side effects like nephrotoxicity. Lungs being the main target organ for TB, a pulmonary route of administration could be an alternative route to overcome such shortcomings. Due to multiple clearance mechanisms and biological barriers that restrict the entry of particles into the respiratory system, the pulmonary route of drug administration may not always be efficient. Thus, the era of nanotechnology has emerged as one of the most promising approaches to developing various drugs for overcoming such challenges. This review article highlights the anatomy and physiology of the lungs, the barriers to the pulmonary drug delivery system, and how these barriers decide the drug disposition at the target site. In addition, the various properties of the drug delivery systems such as size, shape, and charge have been discussed in the subsections, followed by various formulation-based drug delivery systems for INH, including preclinical investigation studies.