Transport of Glial Cell Line-Derived Neurotrophic Factor into Liposomes across the Blood-Brain Barrier: In Vitro and in Vivo Studies

International Journal of Molecular Sciences

Shaoling Wu²  Guoqi Li¹  Xiao Li²  Caina Lin²  Ding Yu²  Shuo Luan² 

[1] Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, China; E-Mail:;Rehabilitation Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, Guangdong, China; E-Mails:

关键词: glial cell line-derived neurotrophic factor;    target sterically stabilized liposomes;    blood-brain barrier;   

DOI  :  10.3390/ijms15033612

来源: mdpi

【 摘 要 】

Glial cell line-derived neurotrophic factor (GDNF) was encapsulated into liposomes in order to protect it from enzyme degradation in vivo and promote its permeability across the blood-brain barrier (BBB). In this study, GDNF conventional liposomes (GDNF-L) and GDNF target sterically stabilized liposomes (GDNF-SSL-T) were prepared. The average size of liposomes was below 90 nm. A primary model of BBB was established and evaluated by transendothelial electrical resistance (TEER) and permeability. This BBB model was employed to study the permeability of GDNF liposomes in vitro. The results indicated that the liposomes could enhance transport of GDNF across the BBB and GDNF-SSL-T had achieved the best transport efficacy. The distribution of GDNF liposomes was studied in vivo. Free GDNF and GDNF-L were eliminated rapidly in the circulation. GDNF-SSL-T has a prolonged circulation time in the blood and favorable brain delivery. The values of the area under the curve (AUC_{(0–1 h)}) in the brain of GDNF-SSL-T was 8.1 times and 6.8 times more than that of free GDNF and GDNF-L, respectively. These results showed that GDNF-SSL-T realized the aim of targeted delivery of therapeutic proteins to central nervous system.

【 授权许可】

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