Sohail Saba, Shah Fawad Ali, Zaman Shahiq Uz, Almari Ali H, Malik Imran, Khan Saifoor Ahmad, Alamro Abir Abdullah, Zeb Alam, Din Fakhar Ud
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Nanomedicine Research Group, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Heliyon. 2023 Sep 3;9(9):e19779. doi: 10.1016/j.heliyon.2023.e19779. eCollection 2023 Sep.
The current study explores the potential of melatonin (MLT)-loaded solid lipid nanoparticles (MLT-SLNs) for better neuroprotective effects in ischemic stroke. MLT-SLNs were prepared using lipid matrix of palmityl alcohol with a mixture of surfactants (Tween 40, Span 40, Myrj 52) for stabilizing the lipid matrix. MLT-SLNs were tested for physical and chemical properties, thermal and polymorphic changes, drug release and neuroprotective studies in rats using permanent middle cerebral artery occlusion (-MCAO) model. The optimized MLT-SLNs showed particle size of ∼159 nm, zeta potential of -29.6 mV and high entrapment efficiency ∼92%. Thermal and polymorphic studies showed conversion of crystalline MLT to amorphous form after its entrapment in lipid matrix. MLT-SLNs displayed a sustained release pattern compared to MLT dispersion. MLT-SLNs significantly enhanced the neuroprotective profile of MLT ascertained by reduced brain infarction, recovered behavioral responses, low expression of inflammatory markers and improved oxidation protection in rats. MLT-SLNs also showed reduced hepatotoxicity compared to -MCAO. From these outcomes, it is evidenced that MLT-SLNs have improved neuroprotection as compared to MLT dispersion and thereby present a promising approach to deliver MLT to the brain for better therapeutic outcomes in ischemic stroke.
本研究探讨了载褪黑素（MLT）的固体脂质纳米粒（MLT-SLNs）在缺血性卒中中发挥更好神经保护作用的潜力。采用棕榈醇脂质基质与表面活性剂混合物（吐温40、司盘40、聚山梨醇酯52）制备MLT-SLNs，以稳定脂质基质。对MLT-SLNs进行了物理和化学性质、热和多晶型变化、药物释放测试，并使用永久性大脑中动脉闭塞（-MCAO）模型在大鼠中进行了神经保护研究。优化后的MLT-SLNs粒径约为159nm，ζ电位为-29.6mV，包封率高达92%。热和多晶型研究表明，MLT包封于脂质基质后，由结晶态转变为无定形态。与MLT分散体相比，MLT-SLNs呈现出缓释模式。通过减少脑梗死、恢复行为反应、降低炎症标志物表达以及改善大鼠氧化保护作用，MLT-SLNs显著增强了MLT的神经保护作用。与-MCAO相比，MLT-SLNs还显示出肝毒性降低。从这些结果可以证明，与MLT分散体相比，MLT-SLNs具有更好的神经保护作用，从而为将MLT输送到大脑以改善缺血性卒中的治疗效果提供了一种有前景的方法。
