title: Targeted delivery of GDNF through the blood-brain barrier by MRI-guided focused ultrasound.
abstract: Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), are promising therapeutic agents for neurodegenerative diseases. However, the application of GDNF to treat these diseases effectively is limited because the blood-brain barrier (BBB) prevents the local delivery of macromolecular therapeutic agents from entering the central nervous system (CNS). Focused ultrasound combined with microbubbles (MBs) using appropriate parameters has been previously demonstrated to be able to open the BBB locally and noninvasively. This study investigated the targeted delivery of GDNF MBs through the BBB by magnetic resonance imaging (MRI)-guided focused ultrasound. Evans Blue extravasation and histological examination were used to determine the optimum focused ultrasound parameters. Enzyme-linked immunosorbent assay was performed to verify the effects of GDNF bound on MBs using a biotin-avidin bridging chemistry method to promote GDNF delivery into the brain. The results showed that GDNF can be delivered locally and noninvasively into the CNS through the BBB using MRI-guided focused ultrasound combined with MBs under optimum parameters. MBs that bind GDNF combined with MRI-guided focused ultrasound may be an effective way of delivering neurotrophic factors directly into the CNS. The method described herein provides a potential means of treating patients with CNS diseases.
authors.affiliation: Department of Ultrasound, Peking University Shenzhen Hospital, Biomedical Research Institute, Shenzhen PKU-HKUST Medical Center, Shenzhen, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Youli
authors.initials: Y
authors.lastname: Cai
authors.forename: Hairong
authors.initials: H
authors.lastname: Zheng
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.forename: Chao
authors.initials: C
authors.lastname: Zou
authors.forename: Chengyu
authors.initials: C
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.forename: Shukun
authors.initials: S
authors.lastname: Lu
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage*; D019220:High-Energy Shock Waves; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D045423:Microbubbles; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor