败血症
活性氧
氧化应激
药理学
肝损伤
药物输送
体内
药品
乙二醇
生物相容性
医学
材料科学
化学
免疫学
生物化学
生物
内科学
纳米技术
冶金
有机化学
生物技术
作者
Chunfang Gan,Hongzhang Deng,Xiang Song,Mingzi Lu,Lei Zhao,Sha Xia,Guoxiang You,Jingxiang Zhao,Yulong Zhang,Anjie Dong,Hong Zhou
出处
期刊:Biomaterials
[Elsevier]
日期:2017-11-01
卷期号:144: 30-41
被引量:82
标识
DOI:10.1016/j.biomaterials.2017.08.008
摘要
Sepsis-associated acute liver injury contributes to the pathogenesis of multiple organ dysfunction syndrome and is associated with increased mortality. Currently, no specific therapeutics for sepsis-associated liver injury are available. With excess levels of reactive oxygen species (ROS) being implicated as key players in sepsis-induced liver injury, we hypothesize that ROS-responsive nanoparticles (NPs) formed via the self-assembly of diblock copolymers of poly(ethylene glycol) (PEG) and poly(propylene sulfide) (PPS) may function as an effective drug delivery system for alleviating sepsis-induced liver injury by preferentially releasing drug molecules at the disease site. However, there are no reports available on the biocompatibility and effect of PEG-b-PPS-NPs in vivo. Herein, this platform was tested for delivering the promising antioxidant therapeutic molecule melatonin (Mel), which currently has limited therapeutic efficacy because of its poor pharmacokinetic properties. The mPEG-b-PPS-NPs efficiently encapsulated Mel using the oil-in-water emulsion technique and provided sustained, on-demand release that was modulated in vitro by the hydrogen peroxide concentration. Animal studies using a mouse model of sepsis-induced acute liver injury revealed that Mel-loaded mPEG-b-PPS-NPs are biocompatible and much more efficacious than an equivalent amount of free drug in attenuating oxidative stress, the inflammatory response, and subsequent liver injury. Accordingly, this work indicates that mPEG-b-PPS-NPs show potential as an ROS-mediated on-demand drug delivery system for improving Mel bioavailability and treating oxidative stress-associated diseases such as sepsis-induced acute liver injury.
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