Reactive oxygen species-responsive HET0016 prodrug-loaded liposomes attenuate neuroinflammation and improve neurological deficit in a rat model of juvenile traumatic brain injury

作者全名："Qin, Jun; Chen, Xiaoli; Wang, Rui; Tian, Zedan; Li, Yang; Shu, Shiyu"

作者地址："[Qin, Jun; Chen, Xiaoli; Tian, Zedan; Shu, Shiyu] Chongqing Med Univ, Dept Anesthesiol, Affiliated Hosp 2, Chongqing, Peoples R China; [Wang, Rui; Li, Yang] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China"

通信作者："Shu, SY (通讯作者)，Chongqing Med Univ, Dept Anesthesiol, Affiliated Hosp 2, Chongqing, Peoples R China."

来源：FRONTIERS IN NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000963002000001

JCR分区：Q2

影响因子：3.2

年份：2023

卷号：17

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：traumatic brain injury; HET0016; neuroinflammation; reactive oxygen species responsive; liposomes

摘要："The arachidonic acid pathway metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to ischemia/reperfusion brain injury. Inhibition of 20-HETE formation can protect the developing brain from global ischemia. In previous studies, we have found that treatment with the 20-HETE synthesis inhibitor N-hydroxy-N-4-butyl-2-methylphenylformamidine (HET0016) can protect the immature brain from traumatic brain injury (TBI), but its hydrophobic nature limits its full potential. We designed a reactive oxygen species-responsive HET0016 prodrug, which consists of a thioketal link between HET0016 and stearyl alcohol (HET-TK-SA), and used the nanoprodrug strategy to successfully synthesize liposomes HET0016 prodrug liposomes (HPLs) to facilitate the application of HET0016 in protection from TBI. HPLs demonstrated spherical shape, size of about 127.8 nm, a zeta potential of -28.8 mv, a narrow particle size distribution and good stability. Male rats at postnatal day 16-17 underwent controlled cortical impact (CCI) followed by intravenous injection with vehicle or HET0016 (1 mg/kg, 2 h post-injury, once/day for 3 days). The results of the in vivo demonstrated that HPLs has good biosafety and can pass through the blood-brain barrier. Not only that compared with HET0016, HPLs better-inhibited inflammation and improved neuronal degeneration, which further led to lesion volume reduction, upgraded behavioral task performance, and ameliorated the degree of TBI impairment. Our results demonstrated HPLs could be a new strategy for juvenile TBI therapy."

基金机构："National Natural Science Foundation of China [82071377]; Chongqing Science and Technology Commission Grants of China [cstc2015jcyjA10095]; Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau) [2022GDRCO02]; sixth batch of Young and Middle-aged High-level Medical Talents Training Project of Chongqing Municipal Health Commission; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China"

基金资助正文："This work was supported by the National Natural Science Foundation of China (No. 82071377), Chongqing Science and Technology Commission Grants of China (No. cstc2015jcyjA10095), and Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau) (No. 2022GDRCO02). This study was partly supported by the sixth batch of Young and Middle-aged High-level Medical Talents Training Project of Chongqing Municipal Health Commission, and Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China."