Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Department of Pharmacy, Kohat University of Science and Technology, Kohat, Pakistan.
Int J Pharm. 2021 Jun 15;603:120670. doi: 10.1016/j.ijpharm.2021.120670. Epub 2021 May 5.
The present study aims to develop curcumin-loaded nanostructured lipid carriers (CUR-NLCs) and investigate their neuroprotective effects in lipopolysaccharide (LPS)-induced depression and anxiety model. Nanotemplate engineering technique was used to prepare CUR-NLCs with Compritol 888 ATO and oleic acid as solid and liquid lipid, respectively. Poloxamer 188, Tween 80 and Span 80 were used as stabilizing agents for solid-liquid lipid core. The physicochemical parameters of CUR-NLCs were determined followed by in vitro drug release and in vivo neuroprotective activity in rats. The optimized CUR-NLCs demonstrated nanometric particle size of 147.8 nm, surface charge of -32.8 mV and incorporation efficiency of 91.0%. CUR-NLCs showed initial rapid followed by a sustained drug release reaching up to 73% after 24 h. CUR-NLCs significantly elevated struggling time and decreased immobility time in forced swim and tail suspension tests. A substantial increase in time spent and number of entries into the light and open compartments was observed in light-dark box and elevated plus maze models. CUR-NLCs improved the tissue architecture and suppressed the expression of p-NF-κB, TNF-α and COX-2 in brain tissues from histological and immunohistochemical analysis. CUR-NLCs improved the neuroprotective effect of curcumin and can be used as a potential therapeutics for depression and anxiety.
本研究旨在制备负载姜黄素的纳米结构脂质载体(CUR-NLCs),并研究其在脂多糖(LPS)诱导的抑郁和焦虑模型中的神经保护作用。采用纳米模板工程技术,以 Compritol 888 ATO 和油酸分别为固体和液体脂质,制备 CUR-NLCs。泊洛沙姆 188、吐温 80 和司盘 80 用作固-液脂质核心的稳定剂。测定 CUR-NLCs 的理化参数,然后进行体外药物释放和大鼠体内神经保护活性研究。优化后的 CUR-NLCs 表现出纳米级粒径为 147.8nm、表面电荷为-32.8mV 和包封效率为 91.0%。CUR-NLCs 表现出初始快速随后持续的药物释放,24 小时后达到 73%。CUR-NLCs 显著增加强迫游泳和悬尾试验中的挣扎时间,减少不动时间。在明暗箱和高架十字迷宫模型中,观察到光暗箱和开室的时间显著增加,进入次数增加。CUR-NLCs 改善了脑组织的组织结构,抑制了脑组织中 p-NF-κB、TNF-α 和 COX-2 的表达,从组织学和免疫组织化学分析。CUR-NLCs 提高了姜黄素的神经保护作用,可作为治疗抑郁和焦虑的潜在疗法。