ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy.
10.1016/j.apsb.2022.09.019
- Author:
Zheng ZHOU
1
;
Keying LI
1
;
Yongchao CHU
1
;
Chao LI
1
;
Tongyu ZHANG
1
;
Peixin LIU
1
;
Tao SUN
1
;
Chen JIANG
1
Author Information
1. Department of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai 201203, China.
- Publication Type:Journal Article
- Keywords:
Epilepsy;
Gliosis;
Inflammation;
Neuroprotection;
Polymeric micelle;
Reactive oxygen species
- From:
Acta Pharmaceutica Sinica B
2023;13(3):1246-1261
- CountryChina
- Language:English
-
Abstract:
As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.
