Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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利奈唑胺纳米颗粒在肺部治疗中的肺部递送：设计，开发和优化

目的

本研究旨在开发和优化负载利奈唑胺的壳聚糖纳米颗粒用于肺部递送。目的是使纳米颗粒的平均粒径小于300 nm，质量中位数空气动力学直径（MMAD）小于5μm，并维持药物释放长达24 h。

方法

通过使用壳聚糖和三聚磷酸钠（STPP）的离子凝胶技术制备了利奈唑胺纳米颗粒。依次使用3 ²全因子设计和合意函数来量化自变量对因变量的影响并优化配方。

结果

初步研究表明，壳聚糖的浓度和STPP的浓度对平均粒径和包封率有显着影响，因此在析因设计中被选作自变量。对3 ²全因子设计的统计分析表明，每个自变量对因变量具有显着影响（p  <  0.05）。

结论

具有期望值0.8193的优化配方显示平均粒径为91.40 nm，MMAD为3.19μm，并在模拟肺液中维持长达24小时的药物释放。然而，需要进一步的体内研究以设计合适的剂量方案并确定纳米颗粒的命运，以安全有效地递送药物。