title: Enhanced neuroprotective effects of resveratrol delivered by nanoparticles on hydrogen peroxide-induced oxidative stress in rat cortical cell culture.
abstract: Resveratrol (RES) has recently been reported as a potential antioxidant in treatment of ischemia/reperfusion injury through attenuating oxidative stress and apoptosis. However, application of RES is limited for its insolubility and short half-time. Latest evidence raises the possibility of developing nanoparticle-based delivery systems with improved solubility, stability and cytotoxicity of lipophilic drug. Here, we reported first a simple way to produce RES-loaded nanoparticles (RES-NPs) based on poly(N-vinylpyrrolidone)-b-poly(ε-caprolactone) polymer and further evaluated the protective effect of RES-NPs on hydrogen peroxide-induced oxidative stress and apoptosis in rat cortical cell culture. The controlled release pattern of RES-loaded nanoparticles was characterized by in vitro release experiments. Cytotoxicity tests proved cytocompatibility of these nanoparticles with neurons. Shown by coumarin-6 loaded nanoparticles, the uptake of nanoparticles by neurons was considered through endocytosis, which could lead to higher uptake efficiency at lower concentration. Thereby, the hypothesis is raised that RES-NPs could demonstrate enhanced neuroprotection compared to an equivalent dose of free RES at lower concentration, especially. It was further supported by enhanced reduction of LDH release, elimination of ROS and MDA, and attenuation of apoptosis signal (ratio of Bax/Bcl-2, activation of caspase-3). RES-NPs could be a potential treatment needing intensive research for ischemia/reperfusion related disorder including stroke.
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, P. R. China. njluxiaowei@163.com
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Lu
authors.forename: Huae
authors.initials: H
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Zhenshu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Donghui
authors.initials: D
authors.lastname: Zheng
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D016503:Drug Delivery Systems; D006861:Hydrogen Peroxide / Q000494:pharmacology; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018384:Oxidative Stress / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry; D011205:Povidone / Q000031:analogs & derivatives / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D018696:Neuroprotective Agents; D011091:Polyesters; D017382:Reactive Oxygen Species; D013267:Stilbenes; C550000:poly(N-vinylpyrrolidone)-b-poly(epsilon-caprolactone); D006861:Hydrogen Peroxide; D011205:Povidone; D000077185:Resveratrol