Lung-Targeted Solid Lipid Nanoparticles for Enhanced Pulmonary Delivery of Anti-Tubercular Drugs: A Novel Approach to Improve Bioavailability

Paulami Pal¹, Subhabrata Ray², Anup Kumar Das³, Manjir Sarma Kataki¹, Saurav Dey⁴, Partha Pratim Dutta⁵, Tumpa Sarkar¹, Mohini Singh¹, Niva Rani Gogoi¹, Bhaskar Mazumder¹*

Solid lipid nanoparticles improved anti-tubercular drug encapsulation, stability, and lung retention, offering a promising targeted pulmonary delivery approach for tuberculosis treatment.

Abstract

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a highly infectious airborne disease affecting one-third of the global population and causing over one million deaths annually. While primarily targeting the lungs, TB can affect multiple organs, posing a significant global health burden. This study explores lipid drug conjugation as a novel targeted therapy for TB. Aerosolization or inhalation of lipid nanoparticle-based colloidal systems offers a promising approach for pulmonary drug delivery, directly targeting the lungs, where TB infection originates. Methods: A tripartite solid lipid nanoparticle (SLN)-based anti-TB formulation was developed using the solvent diffusion technique for prolonged lung delivery. This combination therapy incorporated Isoniazid (INH), Rifampicin (RIF), and Pyrazinamide (PYZ)—the gold-standard TB treatment regimen. Results: The formulated SLNs demonstrated an encapsulation efficiency of 40.53% to 63.73%. Physicochemical characterization, including particle size analysis and transmission electron microscopy (TEM), confirmed spherical nanoparticles with a smooth surface, measuring between 345.0 nm and 640.6 nm. The drug release profile was pH-dependent. Notably, SLNs exhibited exceptional long-term stability. In vivo studies revealed prolonged lung retention compared to nebulized nasal solutions, indicating effective pulmonary targeting and sustained drug release in the bronchiole tree. Conclusion: The developed lipoidal nanoparticles enhanced the biopharmaceutical properties of anti-TB drugs, offering a promising strategy for targeted pulmonary therapy.

Keywords: Solid lipid nanoparticles, Pulmonary drug delivery, Tuberculosis treatment, Rifampicin bioavailability, Inhalable nano-formulation

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