Tuberculosis (TB) is a major cause of preventable deaths and a chronic worldwide health concern. Pulmonary delivery of drugs via inhalable routes has been recommended over systemic administration (such as intravenous or oral) in order to achieve localised distribution of drugs to the lung with enhanced therapeutics and lowered systemic adverse effects. The combination of multiple drugs loaded nanoparticles in a single dosage form like DPI offers a unique therapeutic advantage for simultaneously delivering drug payloads to the intracellular infection sites in predefined ratios. The study aimed to co-administer four WHO-recommended anti-TB drugs, isoniazid, rifampicin, pyrazinamide, and moxifloxacin Hcl, using a sodium alginate polymeric nanoparticle DPI to facilitate their pulmonary administration for effective treatment of TB-infected individuals. The ATDs (isoniazid, rifampicin, pyrazinamide, and moxifloxacin Hcl) loaded sodium alginate nanoparticle separately was prepared using the Emulsification/internal gelation technique. The percentage drug entrapment, drug loading and particle size were of isoniazid nanoparticles, rifampicin nanoparticles, Pyrazinamide nanoparticles and moxifloxacin Hcl nanoparticles were observed to be 76.632±0.448%, 75.260±0.101%, 76.797±0.293%, 77.252±0.086%; 21.261±0.254%, 32.036±0.352%, 14.196±0.458%, 16.480±0.017%; 199.167 ±0.777nm, 221.77 ±1.645nm, 273.157 ±4.117nm and 250.327 ±0.818nm. The PDI of the all four nanoparticles' formulations was observed to be less than 0.2, while high zeta potential value indicated the stability of the formulation. The FTIR, XRD and DSC study confirmed the encapsulation of drug in the nanoparticles. TEM Images confirmed the spherical shape of drug loaded nanoparticles. In the next step, all four ATDs nanoparticles were combined, mixed with the carriers (lactose, leucin, and mannitol), and transformed in the DPI formulation. The lactose containing nanoparticles DPI formulation yielded the better flow property. In vitro drug release study demonstrated that the ATDs combined nanoparticle DPI formulation yielded the sustained release profile of the drug than the blend of the API. In vivo pharmacokinetic study demonstrated the mean residence time (MRT) of a combination of ATDs loaded DPI formulation was between 34-46 hours. Furthermore, an increase in AUC value in the lung for the combination of ATDs loaded DPI formulation compared with the AUC of blend of ATDs DPI. The increase in AUC of the ATDs combined nanoparticle DPI formulation could be attributed, at least in part, to the prolonged retention and reduced alveolar clearance of drug-loaded nanoparticles from lung tissue compared to blend of ATDs drug DPI.
Keywords: ATDs: Antituberculosis drug, DPI: Dry powder inhaler, TB: Tuberculosis, AM: Alveolar microphases, INH: Isoniazid, PZA: Pyrazinamide, RIF: Rifampicin and MHCl: Moxifloxacin hydrochloride.
How to cite this article: Singh P, Kumar B, Verma SK, Sodium Alginate Nanoparticle Dry Powder Inhaler for Pulmonary Co-Delivery of WHO-Recommended Anti-Tuberculosis Medications. Int J Drug Deliv Technol. 2026;16(2s): 587-609; DOI: 10.25258/ijddt.16.587-609