Pharmacokinetics and in vivo distribution of optimized PLGA nanoparticles for pulmonary delivery of levofloxacin

Abstract

Objectives: The aim of this study was to develop and optimize levofloxacin loaded PLGA nanoparticles (LN) for pulmonary delivery employing screening and experimental design and evaluate their in-vitro and in-vivo performance. The objective was to achieve Mass Median Aerodynamic Diameter (MMAD) of LN of less than 5μm, sustain the drug release up to 120 h and a higher AUC/MIC at the site of action. Methods: LN were prepared by modified emulsion solvent evaporation technique employing high speed homogenization, probe sonication and subsequent lyophilization. Key Findings: The Pareto chart from Placket Burman screening design revealed that homogenization speed and amount of PLGA were found to be significant (P < 0.05). Further analysis by 3 full-factorial design revealed that F-ratio was found to be far greater than the theoretical value (P < 0.05) for each regression model. Conclusion: The optimized formulation with desirability value 0.9612 showed mean particle size of 146 nm, MMAD of 4.40 μm and sustained the drug release up to 120 h in simulated lung fluid. Augmentation in Cmax (1.71-fold), AUC 0-∞ (5.46-fold), Mean Residence Time (6.64-fold) and AUC/MIC (6.21-fold) of LN through pulmonary route was found to significantly higher (P < 0.05) than levofloxacin (p. o.).