A review on recent advances in lipid-based drug delivery systems for tuberculosis.

Tuberculosis (TB) remains a global health challenge, as current therapeutic strategies, albeit effective, require prolonged treatment durations and strict patient adherence. This often results in treatment failure and contributes to the growing issue of antibiotic resistance. To address these challenges, extensive research has focused on innovative drug delivery systems to improve bioavailability, enhance site-specific targeting, and overcome the limitations of conventional TB treatment. In this review, we summarise recent advancements in solid lipid nanoparticles, nanostructured lipid carriers (NLCs), and functionalized lipid nanoparticles for TB treatment. A literature review was conducted focusing on the pathophysiology of TB, in vitro and in vivo efficacy, and toxicity of lipid nanoparticles, and recent advancements in lipid nanoparticles for anti-TB drug delivery to the lungs. Studies demonstrated lipid nanoparticles significantly improve the solubility, stability, and targeted delivery of anti-TB drugs to infected macrophages. Rifampicin-loaded NLCs exhibited over 90% drug release sustained over 7 days and remained physically stable for up to 6 months. Mannose-functionalized NLCs showed around 70% macrophage uptake, doubling the rate of non-functionalized systems. In vivo studies on isoniazid-loaded SLNs reported a 3-fold increase in LD₅₀ and a> 26-fold enhancement in bioavailability. Mannosylated clofazimine-NLCs exhibited prolonged lung retention and significantly reduced hepatic and renal toxicity. These quantitative improvements highlight the potential of lipid-based systems to outperform conventional formulations in both efficacy and safety. These advancements demonstrate strong potential for clinical translation, offering a more effective and patient-friendly approach to TB treatment.