Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Abstract

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.

Rifampicin–Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation

“…Liposomes have been tested with various drugs, and liposome-formulated drugs are now in clinical use for cancer and systemic or local infections, as well as for the treatment of chronic respiratory conditions [ 5 ]. Antibiotics encapsulated in liposomes have been shown to be effective both in tuberculous [ 6 ] and in non-tuberculous mycobacteria strains [ 7 ]. The currently available guidelines state that there are no specific treatments, treatment combinations, or therapeutic regimens with proven efficacy [ 8 ].…”

Antituberculosis Targeted Drug Delivery as a Potential Future Treatment Approach

“…Since tissues infected by bacteria can also cause increased vascular permeability through inflammation, the EPR effect is stipulated to occur in such tissues [ 45 ]. Nanoparticles with longer half-lives would hence have a higher chance to be retained at infected tissues [ 46 ].…”

“…One of the approaches to actively deliver the drugs is by the incorporation of macrophages. As Mtb mainly resides in macrophages [ 46 ], using characteristic receptors on macrophages as candidates for active targeting is theoretically feasible and ensures a higher amount of the drug can be delivered to Mtb compared with the free drug or passive targeting [ 64 ]. A broad range of receptors have been recognized on macrophages, and several of them have been investigated for possible uses as target receptors.…”

“…The folate receptor acts as a mediator for the endocytosis of folic acid, an essential vitamin for synthesizing nucleic acid and amino acid necessary for cell division. The folate receptor is a well-known biomarker of cancer cells and has been used broadly as a target for delivery of therapeutic agents for cancer due to its overexpression on cancer cells [ 46 ]. However, this is not unique to cancer cells as folate receptors are also upregulated in macrophages that are involved in inflammatory and autoimmune diseases [ 46 , 68 ].…”

“…The folate receptor is a well-known biomarker of cancer cells and has been used broadly as a target for delivery of therapeutic agents for cancer due to its overexpression on cancer cells [ 46 ]. However, this is not unique to cancer cells as folate receptors are also upregulated in macrophages that are involved in inflammatory and autoimmune diseases [ 46 , 68 ]. A study by Shah et al has investigated the possible delivery of chitosan-folate decorated rifampicin-loaded oleic acid-nanoemulsions by nebulization.…”