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J Control Release. 2018 May 10;277:173-182. doi: 10.1016/j.jconrel.2018.03.019. Epub 2018 Mar 26.

A brain targeting functionalized liposomes of the dopamine derivative N-3,4-bis(pivaloyloxy)-dopamine for treatment of Parkinson's disease.

Author information

1
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
2
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: zrzzl@vip.sina.com.
3
College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China. Electronic address: ling.zhang@manchester.ac.uk.

Abstract

Parkinson's disease (PD) remains one of the most common neurodegenerative movement disorders with limited treatment options available. A dopamine derivative N-3,4-bis(pivaloyloxy)-dopamine (BPD) previously developed in our group has demonstrated superior therapeutic outcome compared to levodopa in a PD mice model. To further improve the therapeutic performance of BPD, a brain targeted drug delivery system was designed using a 29 amino-acid peptide (RVG29) derived from rabies virus glycoprotein as the targeting ligand. RVG29 functionalized liposomes (RVG29-lip) showed significantly higher uptake efficiency in murine brain endothelial cells and dopaminergic cells, and high penetration efficiency across the blood brain barrier (BBB) in vitro. In vivo and ex vivo distribution studies demonstrated RVG29-lip selectively distributed to the brain, striatum and substantia nigra. Furthermore, BPD loaded RVG29-lip (BPD-RVG29-lip) exhibited improved therapeutic efficacy in a PD mouse model, while causing no obvious systemic toxicity after intravenous administration. Thus, BPD-RVG29-lip represents a highly promising approach for the brain targeted treatment of PD.

KEYWORDS:

Brain targeting; Liposomes; N-3,4-bis(pivaloyloxy)-dopamine; Parkinson's disease; RVG29

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