Gene therapy using lactoferrin-modified nanoparticles in a rotenone-induced chronic Parkinson model

Huang, Rongqin; Ke, Weilun; Liu, Yang; Wu, Dongdong; Feng, Linyin; Jiang, Chen; Pei, Yuanying

doi:10.1016/j.jns.2009.09.032

« Previous Next »Journal of the Neurological Sciences
Volume 290, Issue 1 , Pages 123-130, 15 March 2010

Gene therapy using lactoferrin-modified nanoparticles in a rotenone-induced chronic Parkinson model

Rongqin Huang
- Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China
Weilun Ke
- Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China
Yang Liu
- Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China
Dongdong Wu
- Department of Neuropharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Linyin Feng
- Department of Neuropharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Chen Jiang
- Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China
- Corresponding author. Address: Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Pudong, Shanghai, 201203, China. Tel./fax: +86 21 51980079.
Yuanying Pei
- Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China

Received 5 August 2009; received in revised form 26 September 2009; accepted 28 September 2009. published online 12 November 2009.

Abstract

Background

Gene therapy is considered one of the most promising approaches to develop an effective treatment for Parkinson's disease (PD). The existence of blood-brain barrier (BBB) significantly limits its development. In this study, lactoferrin (Lf)-modified nanoparticles (NPs) were used as a potential non-viral gene vector due to its brain-targeting and BBB-crossing ability.

Methods and results

The neuroprotective effects were examined in a rotenone-induced chronic rat model of PD after treatment with NPs encapsulating human glial cell line-derived neurotrophic factor gene (hGDNF) via a regimen of multiple dosing intravenous administration. The results showed that multiple injections of Lf-modified NPs obtained higher GDNF expression and this gene expression was maintained for a longer time than the one with a single injection. Multiple dosing intravenous administration of Lf-modified NPs could significantly improve locomotor activity, reduce dopaminergic neuronal loss, and enhance monoamine neurotransmitter levels on rotenone-induced PD rats, which indicates its powerful neuroprotective effects.