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脑靶向递送姜黄素的固体脂质纳米粒和纳米结构脂质载体的制备、优化及药代动力学评价。

Brain Delivery of Curcumin Using Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Preparation, Optimization, and Pharmacokinetic Evaluation.

机构信息

Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran 14174 , Iran.

Department of Pharmaceutics, School of Pharmacy , Shiraz University of Medical Sciences , Shiraz 45139-56184 , Iran.

出版信息

ACS Chem Neurosci. 2019 Jan 16;10(1):728-739. doi: 10.1021/acschemneuro.8b00510. Epub 2018 Oct 24.

Abstract

Curcumin is a multitherapeutic agent with great therapeutic potential in central nervous system (CNS) diseases. In the current study, curcumin was encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for the purpose of increasing brain accumulation. The preparation processes have been optimized using experimental design and multiobjective optimization methods. Entrapment efficiency of curcumin in SLNs and NLCs was found to be 82% ± 0.49 and 94% ± 0.74, respectively. The pharmacokinetic studies showed that the amount of curcumin available in the brain was significantly higher in curcumin-loaded NLCs (AUC = 505.76 ng/g h) compared to free curcumin (AUC = 0.00 ng/g h) and curcumin-loaded SLNs (AUC = 116.31 ng/g h) ( P < 0.005), after intravenous (IV) administration of 4 mg/kg dose of curcumin in rat. The results of differential scanning calorimetry and X-ray diffraction showed that curcumin has been dispersed as amorphous in the nanocarriers. Scanning electron microscopy images confirmed the nanoscale size and spherical shape of the nanoparticles. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging study indicated that preparation processes do not have any significant effect on the antioxidant activity of curcumin. The results of this study are promising for the use of curcumin-loaded NLCs in more studies and using curcumin in the treatment of CNS diseases.

摘要

姜黄素是一种具有巨大治疗潜力的多治疗剂,可用于中枢神经系统 (CNS) 疾病。在本研究中,为了增加脑内积累,将姜黄素包封于固体脂质纳米粒 (SLNs) 和纳米结构脂质载体 (NLCs) 中。使用实验设计和多目标优化方法对制备过程进行了优化。发现姜黄素在 SLNs 和 NLCs 中的包封效率分别为 82%±0.49%和 94%±0.74%。药代动力学研究表明,与游离姜黄素 (AUC=0.00ng/g h) 和姜黄素负载的 SLNs (AUC=116.31ng/g h) 相比,静脉注射 (IV) 4mg/kg 剂量的姜黄素后,载姜黄素的 NLCs 中脑内可利用的姜黄素量明显更高 (AUC=505.76ng/g h) (P<0.005)。差示扫描量热法和 X 射线衍射结果表明,姜黄素在纳米载体中呈无定形分散。扫描电子显微镜图像证实了纳米粒子的纳米级尺寸和球形形状。DPPH(2,2-二苯基-1-苦基肼基)自由基清除研究表明,制备过程对姜黄素的抗氧化活性没有任何显著影响。这项研究的结果为使用载姜黄素的 NLCs 进行更多研究以及使用姜黄素治疗 CNS 疾病提供了希望。

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