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The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain

Paper ID Volume ID Publish Year Pages File Format Full-Text
11352 734 2008 9 PDF Available
Title
The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain
Abstract

Development of an efficient gene vector is a key-limiting factor of brain gene therapy. In this study, lactoferrin (Lf), for the first time, was investigated as a brain-targeting ligand in the design of polyamidoamine (PAMAM)-based non-viral gene vector to the brain. Using polyethyleneglycol (PEG) as a spacer, PAMAM–PEG–Lf was successfully synthesized. This vector showed a concentration-dependent manner in the uptake in brain capillary endothelial cells (BCECs). The brain uptake of PAMAM–PEG–Lf was 2.2-fold compared to that of PAMAM–PEG–transferrin (Tf) in vivo. The transfection efficiency of PAMAM–PEG–Lf/DNA complex was higher than that of PAMAM–PEG–Tf/DNA complex in vitro and in vivo. The results of frozen sections showed the widespread expression of an exogenous gene in mouse brain via intravenous administration. With a PAMAM/DNA weight ratio of 10:1, the brain gene expression of the PAMAM–PEG–Lf/DNA complex was about 2.3-fold when compared to that of the PAMAM–PEG–Tf/DNA complex. These results provide evidence that PAMAM–PEG–Lf can be exploited as a potential non-viral gene vector targeting to the brain via noninvasive administration. Lf is a promising ligand for the design of gene delivery systems targeting to the brain.

Keywords
Brain targeting; Lactoferrin; Receptor-mediated gene delivery; Polyamidoamine
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 29, Issue 2, January 2008, Pages 238–246
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us