Revolutionizing Tuberculosis Treatment: Emerging Inhalable and Nanoformulation Delivery Systems

Inhalable aerosols and nanoformulation platforms now promise improved lung deposition and reduced systemic toxicity for pulmonary tuberculosis therapies. Direct pulmonary delivery increases intralesional exposure and raises drug concentrations inside granulomas and macrophages. Clinically, these platforms could enable higher local efficacy with lower systemic adverse effects; device characteristics therefore matter when selecting and deploying therapies.

Systemic multidrug regimens deliver broad exposure but often fail to reach necrotic lesion cores. Oral dosing raises systemic toxicity and constrains achievable intralesional concentrations. Device–drug co-design, manufacturing feasibility, adherence, and model-informed PK/PD now drive translation decisions and frame the inhalable platforms and nanocarriers described below.

Dry powder inhalers, nebulizers and breath-actuated devices, spray-dried powders, and liposomal nebulized suspensions are the principal inhalable platforms. Particle aerodynamic size and density determine alveolar deposition and retention; lipid formulations favor macrophage fusion and intracellular delivery, while polymeric matrices control release and enhance stability. Device selection, dosing frequency, and patient inhalation technique will influence clinical performance during early adoption.

Liposomes, polymeric nanoparticles, nanoemulsions, and stimuli-responsive carriers improve lesion targeting and intracellular delivery through enhanced uptake and controlled release. These systems reduce systemic exposure, enable potential long-acting depot effects, and bias uptake toward alveolar macrophages. Human outcome data remain limited, so these advantages are promising but not yet definitive. Translational priorities include scalability, formulation stability, and compatibility with inhalation devices.

Regulatory frameworks create complexity for device–drug combination approvals and require integrated CMC and clinical evidence. Aerosol stability, dose uniformity, and manufacturing scale-up are recurrent hurdles for inhalables and nanocarriers. Model-informed PK/PD can de-risk dosing decisions but cannot substitute randomized endpoints that focus on culture conversion and relapse.

Safety, regulatory, and operational barriers are surmountable and point toward achievable near-term milestones such as standardized CMC packages and early human deposition studies. Over the next 12–24 months, coordinated device–drug development and clinician engagement could make inhalable TB therapies a feasible addition to the treatment armamentarium.

Key Takeaways:

• Screen patients for device suitability and inspiratory capacity when considering inhalable investigational TB therapies.
• Prioritize trial enrollment for patients with cavitary pulmonary disease and those at high risk of systemic toxicity.
• Incorporate model-informed PK/PD into early dosing plans and monitor device lot performance in phase I/II trials.