Studies in Development and Statistical Optimization of Levofloxacin Solid Lipid Nanoparticles for the Treatment of Tuberculosis

Background WHO acclaims superiority of levofloxacin for the treatment of drug-resistant tuberculosis. Purpose The purpose of this research was to develop levofloxacin-loaded solid lipid nanoparticles (LEV-SLN) for use in tuberculosis treatment. The goal was to make LEV-SLN with a mean particle size of less than 300 nm, a drug release duration of more than 12 h, and an LEV-SLN MMAD of less than 5 mu m. Methods LEV-SLN was made using a single emulsification process, followed by solvent evaporation and lyophilization. A Plackett-Burman screening design and a 3(2) full factorial design were employed sequentially to explore the impact of various formulation and process parameters on mean particle size, % entrapment efficiency, and in vitro drug release. Results According to the Pareto chart from the Plackett-Burman screening design, the amount of poloxamer and homogenization speed had a significant influence on the mean particle size (p < 0.05). LEV-SLN had a minimum inhibitory concentration of 0.7 mu g/ml, whereas pure drug had a minimum inhibitory value of 1.0 mu g/ml. The F-ratio for each model developed was higher than the theoretical value (p < 0.05) in a follow-up analysis employing 3(2) full factorial design, showing that each model was significant. Conclusion The best formulation had a mean particle size of 79.70 nm, lasted 12 h in simulated lung fluid, and had an MMAD of 3.71 mu m, confirming that the drug may reach up to deep lungs. In the future, preclinical study is needed to develop a realistic dosing regimen and determine the pharmacokinetics and pharmacodynamics of LEV-SLN.