Pulmonary Delivery of Linezolid Nanoparticles for Treatment of Tuberculosis: Design, Development, and Optimization

Abstract

The present study was aimed to develop and optimize linezolid loaded chitosan nanoparticles for pulmonary delivery. The objective was to achieve the mean particle size of nanoparticles less than 300 nm and the mass median aerodynamic diameter (MMAD) less than 5 μm and sustain the drug release up to 24 h. Linezolid nanoparticles were prepared by ionic gelation technique employing chitosan and sodium tripolyphosphate (STPP). A 32 full factorial design and desirability function were sequentially used to quantify the effect of independent variables on dependent variables and optimize the formulation. The preliminary studies suggested that the concentration of chitosan and concentration of STPP had an appreciable effect on mean particle size and percentage entrapment efficiency and hence were selected as independent variables in a factorial design. Statistical analysis of 32 full factorial design revealed that each independent variable had a significant effect (p < 0.05) on the dependent variables. The optimized formulation with desirability value 0.8193 showed a mean particle size of 91.40 nm, MMAD of 3.19 μm, and sustained the drug release up to 24 h in simulated lung fluid. However, further in vivo studies are required to design suitable dosage regimen and establish the fate of nanoparticles for safe and efficacious delivery of the drug.