Chitosan-Based Linezolid Dry Powder Inhalers: A Novel Approach for Targeted Pulmonary Delivery in Tuberculosis Treatment

Introduction

Tuberculosis (TB) remains one of the leading causes of infectious deaths worldwide, ranking second only to COVID-19. The rise of Multidrug-Resistant (MDR) and Extensively Drug-Resistant (XDR) TB strains highlights the critical need for novel and effective treatment approaches.

Methodology

This research explores a targeted pulmonary drug delivery system using Dry Powder Inhalers (DPI) to administer the antibiotic Linezolid (Lzd) directly to the lungs. Biodegradable Microparticles (MPs) of Linezolid were synthesized using chitosan polymer via spray drying, with Critical Process Parameters (CPPs) such as inlet temperature, aspiration rate, and feed rate optimized to achieve desired Particle Size (PS) and Entrapment Efficiency (%EE). Comprehensive evaluations were conducted, including in vivo studies, stability testing, H37 RV strain sensitivity, particle size distribution, crystallinity, flow properties, and drug-polymer compatibility.

Results and Discussion

The optimized batch of Linezolid (Lzd) MPs exhibited an impressive 89.57% entrapment efficiency with a particle size 3.9 μm. Physically, the MPs were a free-flowing powder with a bulk density of 0.171 g/cm³, tapped density of 0.2287 g/ cm³, Carr’s index of 25%, and Hausner’s ratio of 0.95. These spherical particles demonstrated sustained drug release for up to 12 hr, with a process yield of 75.91% and a moisture content of 1.58%. Importantly, the MPs showed significant inhibitory effects against the H37 RV strain of Mycobacterium tuberculosis across various concentrations. In vivo studies revealed a 55.2% increase in bioavailability with the Lzd DPI formulation, which was 1.25 times higher than the oral tablet.

Conclusion

This novel inhalation system holds the potential to reduce dosing frequency, minimize side effects, and improve patient adherence, offering a promising alternative for effective TB management.