Advanced drug delivery and therapeutic strategies for tuberculosis treatment

Abstract

Tuberculosis (TB) remains a significant global health challenge, necessitating innovative approaches for effective treatment. Conventional TB therapy encounters several limitations, including extended treatment duration, drug resistance, patient noncompliance, poor bioavailability, and suboptimal targeting. Advanced drug delivery strategies have emerged as a promising approach to address these challenges. They have the potential to enhance therapeutic outcomes and improve TB patient compliance by providing benefits such as multiple drug encapsulation, sustained release, targeted delivery, reduced dosing frequency, and minimal side effects. This review examines the current landscape of drug delivery strategies for effective TB management, specifically highlighting lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, emulsion-based systems, carbon nanotubes, graphene, and hydrogels as promising approaches. Furthermore, emerging therapeutic strategies like targeted therapy, long-acting therapeutics, extrapulmonary therapy, phototherapy, and immunotherapy are emphasized. The review also discusses the future trajectory and challenges of developing drug delivery systems for TB. In conclusion, nanomedicine has made substantial progress in addressing the challenges posed by conventional TB drugs. Moreover, by harnessing the unique targeting abilities, extended duration of action, and specificity of advanced therapeutics, innovative solutions are offered that have the potential to revolutionize TB therapy, thereby enhancing treatment outcomes and patient compliance.

Keywords: Drug delivery systems; Extensive drug-resistant tuberculosis; Multidrug-resistant tuberculosis; Nanoparticles; Therapeutics; Tuberculosis.

Fig. 1

Pathogenesis of TB infection. A Pulmonary TB: by inhalation of infected droplet nuclei, M. tuberculosis enters the respiratory tract and alveoli of the lungs. It is ingested by AM, which attempts to destroy the bacilli initially. The development of symbiosis results in logarithmic growth of bacilli. The multicellular host immune response develops, bringing more defensive cells to the site. The infected areas progress into a granuloma that can develop a solid caseous center, where the bacteria survive for years, resulting in latent TB. In the final stage of pathogenesis, liquefaction of the caseous center and granuloma rupture cause the spread of bacilli. Pulmonary TB is caused by bacterial spread in the lungs. Extrapulmonary TB results from the dissemination of bacilli to other tissues and organs via the vascular or lymphatic system. B Extrapulmonary TB; common sites include the pleura, lymph nodes, gastrointestinal tract, urogenital tract, skin, bones, meninges or eye [14, 15]

Fig. 2

Modern drug delivery systems for bioactive molecules in TB treatment. Modern drug delivery strategies for existing TB drugs could be promising, as they can offer the flexibility to adopt better routes of administration, multiple drug encapsulation, sustained drug release, targeted drug delivery, enhanced permeability and retention along with a lower incidence of side effects. A Promising strategies for optimizing drug delivery could be based on liposomes, niosomes, microparticles, microemulsions, nanoemulsions, gold nanoparticles, silica nanoparticles, carbon nanomaterials, polymeric micelles, CD, dendrimers, engineered antigens, hydrogels, and liquid crystals. B The promising preclinical developments for TB treatment involve varying routes of administration, such as oral, intranasal, pulmonary, topical, intramuscular, intravenous and subcutaneous routes. Newer approaches include transdermal patches, floating systems, and a one-time large-dose controlled-release gastrointestinal resident delivery system

Fig. 3

Schematic representation of nonlamellar lyotropic liquid crystalline nanoparticles. A Cationic charge effect on the S. aureus cell membrane. B Chemical structures of monoolein (MO), cationic lipid 1,2-dioleyl-3-trimethyl-ammonium-propane (DOTAP), antibiotic rifampicin (Rif), and Pluronic F127 modified and reprinted with permission from [91] © Elsevier Inc

Fig. 4

Types of gold nanoparticles and synthesis method. Various types of gold nanoparticles are used for the delivery of ATDs. A GNPs are synthesized in various shapes according to the requirements of the delivery system. B The synthesis of nanoparticles follows a systematic sequence of steps and can be surface modified to target the nanoparticle to the desired site. C The systemic administration of GNPs in preclinical models has been found to enhance the efficiency of drug delivery, thereby improving the action of ATDs

Fig. 5

Chemical structures of the MWCNTs conjugated with therapeutic molecules and aspects of the release of cargos. Reprinted from [207] CC BY license

Fig. 6

Possibilities with 3D printing techniques: Various biopolymers and ceramics can be incorporated with therapeutics by utilizing various 3D printing techniques. Modified with permission from [245] © American Chemical Society

Fig. 7

Targeting infected alveolar macrophages (AM). In active targeting, ligands are incorporated into the drug carrier, which interacts with specific receptors on AM, leading to ligand‒receptor-mediated phagocytosis. In passive targeting, the surface of the carrier lacks a host-specific ligand. The macrophage surface receptors that can be utilized for active targeting include the formyl peptide receptor, Toll-like receptor, folate receptor, Fc (fragment, crystallizable) receptor, tuftsin receptor, mannose receptor (CD206), complement receptor, hyaluronic acid receptor (CD44), scavenger receptor, fucosyl receptor, Dectin-1 receptor and lectin-like receptors. Common ligands used to target macrophages include a Mannosylated molecule, b Phosphoserine conjugate, c Folic acid, d Hyaluronic acid, e Tuftsin peptide, f Curdlan (β-1,3 glucose). Concept adopted from [30]