Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson's disease

Abstract

Parkinson's disease (PD), one of the most common movement and neurodegenerative disorders, is challenging to treat, largely because the blood-brain barrier blocks passage of most drugs. Here we find exosomes from blood showing natural brain targeting ability which involved the transferrin-transferrin receptor interaction. Thus, we develop a biocompatible platform based on blood exosomes for delivering drugs across the blood-brain barrier. Blood exosomes show sizes between 40 and 200 nm and spherical morphology, and dopamine can be efficiently loaded into blood exosomes by a saturated solution incubation method. Further in vitro and in vivo studies demonstrates these exosomes successfully delivered dopamine to brain, including the striatum and substantia nigra. Brain distribution of dopamine increased >15-fold by using the blood exosomes as delivery system. Dopamine-loaded exosomes show much better therapeutic efficacy in a PD mouse model and lower systemic toxicity than free dopamine after intravenous administration. These results suggest that blood exosomes can be used as a promising drug delivery platform for targeted therapy against PD and other diseases of the central nervous system.