Department of Chemistry, University of Florence, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Colloids Surf B Biointerfaces. 2018 Jan 1;161:302-313. doi: 10.1016/j.colsurfb.2017.10.062. Epub 2017 Nov 6.
Andrographolide is a major diterpenoid of Andrographis paniculata and possesses several biological activities, including protection against oxidative stress mediated neurotoxicity, inflammation-mediated neurodegeneration, and cerebral ischemia. However, this molecule shows low bioavailability, poor water solubility, and high chemical and metabolic instability. The present study reports preparation of solid lipid nanoparticles (SLN) to deliver andrographolide (AG) into the brain. SLN were prepared using Compritol 888 ATO as solid lipid and Brij 78 as surfactant and applying emulsion/evaporation/solidifying method as preparative procedure. Nanoparticles have a spherical shape, small dimensions, and narrow size distribution. Encapsulation efficiency of AG-loaded SLN was found to be 92%. Nanoparticles showed excellent physical and chemical stability during storage at 4°C for one month. The lyophilized product was also stable at 25°C during the same period. SLN remained unchanged also in the presence of human serum albumin and plasma. In vitro release at pH 7.4 was also studied. The release of AG was prolonged and sustained when the compound was entrapped in SLN. The ability of SLN to cross the blood-brain barrier (BBB) was evaluated first in vitro by applying a permeation test with artificial membrane (parallel artificial membrane permeability assay, PAMPA) to predict passive and transcellular permeability through the BBB, and then by using hCMEC/D3 cells, a well-established in vitro BBB model. In vitro results proved that nanoparticles improved permeability of AG compared to free AG. Fluorescent nanoparticles were then prepared for in vivo tests in healthy rats. After intravenous administration, fluorescent SLN were detected in brain parenchyma outside the vascular bed, confirming their ability to overcome the BBB.
穿心莲内酯是穿心莲的一种主要二萜类化合物，具有多种生物活性，包括预防氧化应激介导的神经毒性、炎症介导的神经退行性变和脑缺血。然而，该分子表现出生物利用度低、水溶性差、化学和代谢稳定性高的特点。本研究报告了使用固体脂质纳米粒 (SLN) 将穿心莲内酯 (AG) 递送至大脑的方法。SLN 是使用 Compritol 888 ATO 作为固体脂质和 Brij 78 作为表面活性剂，并应用乳化/蒸发/固化方法作为制备程序制备的。纳米粒呈球形，尺寸小，粒径分布窄。AG 负载的 SLN 的包封效率为 92%。纳米粒在 4°C 下储存一个月时表现出极好的物理和化学稳定性。在同一时期，冻干产品在 25°C 下也稳定。SLN 在存在人血清白蛋白和血浆的情况下也保持不变。还研究了在 pH 7.4 下的体外释放。当化合物被包封在 SLN 中时，AG 的释放得到了延长和持续。首先通过应用人工膜（平行人工膜渗透性测定法，PAMPA）进行体外透血脑屏障（BBB）能力评估来评估 SLN 穿过血脑屏障的能力，以预测通过 BBB 的被动和细胞间通透性，然后使用 hCMEC/D3 细胞，一种成熟的体外 BBB 模型。体外结果证明，与游离 AG 相比，纳米粒提高了 AG 的通透性。然后为体内试验制备了荧光纳米粒。静脉给药后，在血管床外的脑实质中检测到荧光 SLN，证实了它们克服 BBB 的能力。
