Background: Levofloxacin has been recommended by the WHO for the treatment of
pulmonary tuberculosis and inhalable delivery of levofloxacin can be advantageous over conventional
Objective: This study aimed to develop and optimize inhalable levofloxacin Loaded Chitosan Nanoparticles
(LCN). The objective was to achieve the mean particle size of LCN less than 300nm, sustain
the drug release up to 24 h, and achieve MMAD of LCN of less than 5μm.
Methods: LCN were prepared by ionic gelation of chitosan with sodium tripolyphosphate (STPP)
and subsequent lyophilization. A Plackett Burman screening design, 32 full factorial design, and
overlay plots were sequentially employed to optimize the formulation. The mean particle size, %
entrapment efficiency, in vitro drug release, and minimum inhibitory concentration were all evaluated.
Results: The Pareto chart from the Placket Burman screening design revealed that the concentrations
of chitosan and STPP was found to be significant (p < 0.05). Further analysis by 32 full factorial
design revealed that F-ratio for each model generated was found to be greater than the theoretical
value (p < 0.05), confirming the significance of each model.
Conclusion: The optimized formulation showed a mean particle size of 171.5 nm, sustained the
drug release up to 24 h in simulated lung fluid, and revealed MMAD of 3.18 μm, which can confirm
delivery of the drug to the deep lung region. However, further in vivo studies are required to
design a suitable dosage regimen and establish the fate of nanoparticles for safe and efficacious delivery
of the drug.