AUTHOR=Xu Huae , Hua Ye , Zhong Jie , Li Xiaolin , Xu Wei , Cai Yingyuan , Mao Yukang , Lu Xiaowei 

TITLE=Resveratrol Delivery by Albumin Nanoparticles Improved Neurological Function and Neuronal Damage in Transient Middle Cerebral Artery Occlusion Rats

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.01403

DOI=10.3389/fphar.2018.01403

ISSN=1663-9812

ABSTRACT=Human serum albumin (HSA) is an intrinsic protein and important carrier that transports endogenous as well as exogenous substances. We demonstrated the regional accumulation of albumin in the ischemia-reperfusion (I/R) brain, which providing the footstone for the application of HSA based nanoparticles in study of cerebral I/R injury. Resveratrol is potential in treatment of cerebral I/R injury but restricted for its water insolubility and short half-life in vivo. Herein, we prepared resveratrol (RES)-encapsulated by HSA nanoparticles (RES-HSA-NPs) to facilitate the application of resveratrol in protection from cerebral I/R injury. RES-HSA-NPs demonstrated spherical shape, a diameter about 100 nm, a highest resveratrol encapsulation efficiency of 60.9 ± 5.07%, and controlled release pattern with the maximum release ratio of 50.2 ± 4.91% (in pH=5.0 PBS) and 26. 2 ± 2.73% (in pH=7.4 PBS), respectively, after 90h incubation at 37 °C. After intravenous injection into transient middle cerebral artery occlusion (tMCAO) rats, RES-HSA-NPs improved neurological score and decreased infarct volume at 24 hours after tMCAO in a dose dependent manner. A single dose of 20 mg/Kg RES-HSA-NPs via tail vein improved neurological outcomes and decreased infarct volume at 24 h and 72 h in tMCAO rats. Ischemia-reperfusion increased oxidative stress (indicated by products of lipid peroxidation, MDA) and neuronal apoptosis (indicated by yellow-brown TUNEL-positive cells), 20 mg/Kg of RES-HSA-NPs via tail vein administration significantly attenuated oxidative stress and neuronal apoptosis. These results demonstrated the potential of RES-HSA-NPs in therapy of cerebral ischemia-reperfusion injury.