PDF(Pubmed)
Abstract：
Astaxanthin (ATX) is a carotenoid nutraceutical with poor bioavailability due to its high lipophilicity. We tested a new tailored nanodroplet capable of solubilizing ATX in an oil-in-water micro-environment (LDS-ATX) for its capacity to improve the ATX pharmacokinetic profile and therapeutic efficacy. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile the pharmacokinetics of ATX and LDS-ATX, superoxide mutase (SOD) activity to determine their antioxidant capacity, protein carbonylation and lipid peroxidation to compare their basal and lipopolysaccharide (LPS)-induced oxidative damage, and ELISA-based detection of IL-2 and IFN-γ to determine their anti-inflammatory capacity. ATX and LDS-ATX corrected only LPS-induced SOD inhibition and oxidative damage. SOD activity was restored only by LDS-ATX in the liver and brain and by both ATX and LDS-ATX in muscle. While in the liver and muscle, LDS-ATX attenuated oxidative damage to proteins and lipids better than ATX; only oxidative damage to lipids was preferably corrected by LDS-ATX in the brain. IL-2 and IFN-γ pro-inflammatory response was corrected by LDS-ATX and not ATX in the liver and brain, but in muscle, the IL-2 response was not corrected and the IFN-γ response was mitigated by both. These results strongly suggest an organ-dependent improvement of ATX bioavailability and efficacy by the LDS-ATX nanoformulation.
摘要：
虾青素(ATX)是一类类胡萝卜素营养制品,由于其高的亲脂性而具有差的生物利用度。我们测试了一种能够在水包油微环境（LDS-ATX）中溶解ATX的新型定制纳米液滴，以改善ATX的药代动力学特征和治疗功效。我们使用液相色谱串联质谱（LC-MS/MS）来描述ATX和LDS-ATX的药代动力学，超氧化物变位酶(SOD)活性测定其抗氧化能力,蛋白质羰基化和脂质过氧化，以比较它们的基础和脂多糖（LPS）诱导的氧化损伤，和基于ELISA的IL-2和IFN-γ检测以确定它们的抗炎能力。ATX和LDS-ATX仅校正LPS诱导的SOD抑制和氧化损伤。SOD活性仅通过肝脏和大脑中的LDS-ATX以及肌肉中的ATX和LDS-ATX恢复。在肝脏和肌肉中，LDS-ATX比ATX更好地减弱对蛋白质和脂质的氧化损伤;仅对脂质的氧化损伤优选地被脑中的LDS-ATX校正。IL-2和IFN-γ促炎反应通过LDS-ATX而不是ATX在肝脏和大脑中得到纠正，但是在肌肉中，IL-2应答未得到纠正,IFN-γ应答均得到缓解.这些结果强烈表明LDS-ATX纳米制剂对ATX生物利用度和功效的器官依赖性改善。
