Abstract
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.
Highlights
Neurodegenerative diseases represent a major socioeconomic burden and unimaginable misery for millions of sufferers and their families around the world
When the brain capillary endothelial cells (BCECs)/ACs was confluent, which was judged by transendothelial electrical resistance (TEER) primarily, they were employed as in vitro blood-brain barrier (BBB) model to evaluate the permeability of Glial cell line-derived neurotrophic factor (GDNF) liposomes
The results indicated that the permeability of GDNF was increased after it was incorporated into liposomes and could be increased significantly after it was loaded by sterically stabilized liposomes (SSL)-T
Summary
Neurodegenerative diseases represent a major socioeconomic burden and unimaginable misery for millions of sufferers and their families around the world. GDNF is a distant member of the transforming growth factor β superfamily that was originally isolated from the rat B49 glial cell line [2]. It is expressed throughout the central nervous system (CNS). Parkinson’s disease (PD) is one of the major neurodegenerative disorders in middle and old age This disease arises from a progressive degeneration of dopaminergic neurons in the substantia nigra and is characterized by resting tremor, bradykinesia, rigidity, and postural instability [10]. Many studies, carried out in a wide variety of rodent and primate models of Parkinson’s disease, have demonstrated the efficacy of GDNF [11,12,13], with clinical trials currently in progress [14]. GDNF conventional liposomes (GDNF-L) and GDNF targeted sterically stabilized liposomes (GDNF-SSL-T) were prepared at first, and the permeability of these two GDNF liposomes in vitro BBB model and the uptake in brain in vivo were studied
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