Spray Dried Linezolid-Loaded Inhalable Chitosan Microparticles for Tuberculosis: A QbD-Driven Approach to Enhance Pulmonary Delivery

Tuberculosis (TB) happens to be a major problem in world health. The most worrisome part of TB treatment is dealing with drug-resistant strains, especially multidrug-resistant (MDR) and extensively drug-resistant (XRD) varieties. Conventional anti-TB medication treatment does not affect these. Linezolid offers several advantages, including direct drug delivery to the lungs (site of infection), reducing systemic toxicity when administered orally or intravenously over long periods, and enhancing therapeutic efficacy. Linezolid Microparticles (Lzd MPs) Dry powder Inhalers (DPIs) were synthesized by mixing sodium tripolyphosphate (STPP) with Chitosan using the ionic gelation method to encapsulate the drug to enhance therapeutic action and combined with Spray drying, converts the gelled particles into a fine, respirable powder. Formulation optimization was achieved through 32 full factorial designs and a desirability function. The ideal combination exhibited a particle size and MMAD below 5 μm with a drug release duration of up to 24 h. The factorial design revealed that chitosan and STPP concentrations significantly influenced mean Ps and EE (p < 0.05). The desirability technique yielded an optimal formulation with a value of 0.965, an average particle size of 4.6 μm, and a 24-h drug release. The optimized formulation had an MMAD of 4.2 μm, indicating effective deep lung penetration for TB treatment ensuring effective pulmonary deposition. Additional results included a process yield of 75.91%, a surface charge of − 42.0 mV, and a moisture content of 1.58%. Toxicity studies on L6 cell lines showed dose-dependent toxicity with an IC50 value of 2.46 µg/ml, while histopathological studies revealed no cell irritation or disruption of lung morphology. The optimized formulation demonstrated promising results in terms of particle size, drug release, and safety, although further studies are required to determine the optimal dosage regimen, confirm its clinical efficacy and explore its role in addressing drug resistance in TB, which remains a pressing global health issue.