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 µm.

Methods

LEV-SLN was made using a single emulsification process, followed by solvent evaporation and lyophilization. A Plackett–Burman screening design and a 3² 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 µg/ml, whereas pure drug had a minimum inhibitory value of 1.0 µg/ml. The F-ratio for each model developed was higher than the theoretical value (p < 0.05) in a follow-up analysis employing 3² 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 µm, 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.

Graphical abstract

中文翻译：

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左氧氟沙星固体脂质纳米粒治疗结核病的开发及统计优化研究

背景

世卫组织称赞左氧氟沙星治疗耐药结核病的优越性。

目的

本研究的目的是开发用于结核病治疗的载有左氧氟沙星的固体脂质纳米颗粒 (LEV-SLN)。目标是制造平均粒径小于 300 nm、药物释放时间超过 12 小时、LEV-SLN MMAD 小于 5 µm 的 LEV-SLN。

方法

LEV-SLN 使用单一的乳化工艺制成，然后是溶剂蒸发和冻干。依次采用Plackett-Burman 筛选设计和 3 ²全因子设计来探索各种配方和工艺参数对平均粒径、包封率百分比和体外药物释放的影响。

结果

根据 Plackett-Burman 筛选设计的 Pareto 图，泊洛沙姆用量和均质速度对平均粒径有显着影响（p  < 0.05）。LEV-SLN 的最小抑制浓度为 0.7 µg/ml，而纯药物的最小抑制值为 1.0 µg/ml。^{在采用 3 2}全因子设计 的后续分析中，所开发的每个模型的F比均高于理论值 ( p < 0.05) ，表明每个模型均具有显着性。

结论

最佳配方的平均粒径为 79.70 nm，在模拟肺液中持续 12 小时，MMAD 为 3.71 µm，证实该药物可以到达肺部深处。未来，需要进行临床前研究以制定现实的给药方案并确定 LEV-SLN 的药代动力学和药效学。

图形概要