Recent Developments in Drug Delivery for Treatment of Tuberculosis by Targeting Macrophages

Abstract

Tuberculosis (TB) is among the greatest public health and safety concerns in the 21st century Mycobacterium tuberculosis, which causes TB, infects alveolar macrophages and uses these cells as one of its primary sites of replication. The current TB treatment regimen, which consists of chemotherapy involving a combination of 3-4 antimicrobials for a duration of 6-12 months, is marked with significant side effects, toxicity, and poor compliance. Targeted drug delivery offers a strategy that can overcome many of the problems of current TB treatment by specifically targeting infected macrophages. Recent advances in nanotechnology and material science have opened an avenue to explore drug carriers that actively and passively target macrophages. This approach can increase the drug penetration into macrophages by using ligands on the nanocarrier that interact with specific receptors for macrophages. This review encompasses the recent development of drug carriers specifically targeting macrophages actively and passively. Future directions and challenges associated with development of effective TB treatment are also discussed.

Advanced drug delivery and therapeutic strategies for tuberculosis treatment

“…Recent advances in nanotechnology have brought carriers into the limelight, which can specifically target AM [30]. Modulation of the physical properties of drug carriers, such as surface composition, charge, shape, particle size, hydrophobicity, and zeta potential, can modify drug internalization by AM.…”

“…Strategies that do not rely on specific ligands have been called passive targeting. For passive targeting of AM, polymer-and polysaccharidebased carriers, as well as liposomes, solid lipid nanoparticles (SLNs), and gold nanorods, have been utilized for numerous agents, mostly INH and RIF [30]. Polysaccharides and their derivatives, including chitosan, inulin, alginate, and CD, have seen increased applications owing to their biocompatibility, biodegradability, hydrophilicity, mucoadhesive properties, use in modifying carrier surface charge, and target specificity [63][64][65][66].…”

“…Among polymers, biocompatible PLGA has found profound use in the fabrication of controlled ATD delivery systems because of the ease in achieving the desired dose and release kinetics by modification of the lactide to glycolide ratio, molecular weight, and drug concentration [250][251][252]. With regard to tissue-resident macrophage targeting for the delivery of ATDs, the surface of the drug carrier is functionalized with ligands, including mannosylated molecule, β-glucan, curdlan (β-1,3 glucose), folic acid, hyaluronic acid, tuftsin peptide, and phosphoserine conjugate, that can be recognized by corresponding receptors on macrophages, such as mannosyl receptor (CD206), dectin-1 receptor, folate receptor, tuftsin receptor, hyaluronic acid receptor, fucosyl and scavenger receptor, Fc receptor, transferrin receptor, formyl peptide receptor (FPR), and other lectin-like receptors [30,253,254] represented in Fig. 7.…”

“…By developing inexpensive and easy-to-administer delivery systems that offer extended drug release, dosing frequency could be reduced, thereby improving patient adherence. Direct targeting by selectivity toward both AM and tubercle bacilli may counteract the ability of intracellular pathogens to evade antibiotic treatments [30]. Thus, NDDSs can help optimize drug delivery to the target site, maximizing drug absorption and minimizing unwanted side effects [31].…”

Lipid Nanoparticles as Delivery Vehicles for Inhaled Therapeutics

“…Both passive targeting of alveolar macrophages utilizing receptor-independent uptake pathways and active targeting by incorporating a macrophage-specific cell surface receptor have been explored. This area has been recently reviewed in detail and we will not cover it here [ 87 ].…”