Inhalable Pyrazinamide Loaded Lipid Polymer Hybrid Nanoparticles: In vitro and In vivo Lung Deposition Studies

In the present report, a nanoparticle based inhalable formulation of Pyrazinamide was prepared and evaluated for targeted drug delivery for pulmonary tuberculosis. Lipid polymer hybrid nanoparticles (LPHNs) loaded with pyrazinamide was prepared using emulsion-solvent evaporation technique with further optimization using design of experiments. Amount of polymer and lipid were chosen as the independent factors and particle size, percentage entrapment efficiency, and drug release at 6 hours (D6) were chosen as dependent variables. Optimized batch revealed particle size of 160.9 nm, % entrapment efficiency of 62.34 %, zetapotential of -27.45 mV and in-vitro drug release at 6 h of 75.18 %. The mean aerodynamic diameter of the particles was 0.845 μm which indicates ability to penetrate deep into the lungs. İn vivo deposition studies demonstrated enhanced efficacy of the nano-formulation as compared to pure drug. Stability testing was expedited for the optimized batch of LPHN and the results confirmed no remarkable deviations in the values. Overall, the findings indicate LPHNs made of biodegradable lipid as a viable method for pulmonary drug administration of pyrazinamide.