The potential of duloxetine-loaded solid lipid nanoparticles (DLX-SLNs) for enhanced antidepressant activity was investigated in the current study. Nano-template engineering technology was successfully employed for the preparation of DLX-SLNs. In vivo forced swim and tail suspension tests were used to evaluate behavioral changes of rats in lipopolysaccharide-induced depression. The determination of brain-derived neurotropic factor (BDNF) in brain and plasma was carried out using enzyme-linked immunosorbent assay. The incorporation efficiency of optimized DLX-SLNs formulation was found to be 80 % with particle size of 114.5 nm, PDI of 0.29 and zeta potential of -18.2 mV. Powder X-ray diffractometry and differential scanning calorimetry demonstrated sufficient incorporation into lipid matrix and amorphous behavior of DLX. In vitro release profile of DLX-SLNs showed a sustained release achieving a cumulative amount of 52.97 % for 24 h. DLX-SLNs showed a significant decrease in immobility time in forced swim and tail suspension tests. DLX-SLNs increased BDNF levels in plasma and brain after 2 weeks. Immunohistochemistry results demonstrated significant reduction in the expression of tumor necrosis factor-α and cyclooxygenase enzyme-2 in brain. In conclusion, solid lipid nanoparticles can be utilized as a potential carrier for the delivery of antidepressant drugs into the brain.

在当前研究中，研究了度洛西汀负载的固体脂质纳米颗粒（DLX-SLNs）增强抗抑郁活性的潜力。纳米模板工程技术已成功用于DLX-SLN的制备。体内强迫游泳和尾巴悬吊试验用于评估脂多糖诱导的抑郁症大鼠的行为变化。使用酶联免疫吸附测定法测定脑和血浆中脑源性神经营养因子（BDNF）。发现优化的DLX-SLNs制剂的掺入效率为80％，粒径为114.5 nm，PDI为0.29，ζ电位为-18.2 mV。粉末X射线衍射法和差示扫描量热法证明足够掺入脂质基质和DLX的无定形行为。体外DLX-SLN的释放曲线显示持续释放，在24小时内累计达到52.97％。DLX-SLNs在强迫游泳和尾部悬吊测试中显示出不动时间显着减少。2周后，DLX-SLNs增加血浆和脑中的BDNF水平。免疫组织化学结果显示脑中肿瘤坏死因子-α和环氧合酶-2的表达显着降低。总之，固体脂质纳米颗粒可以用作将抗抑郁药输送到大脑的潜在载体。