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The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain
- Source :
-
Biomaterials . Jan2008, Vol. 29 Issue 2, p238-246. 9p. - Publication Year :
- 2008
-
Abstract
- 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. [Copyright &y& Elsevier]
- Subjects :
- *THERAPEUTICS
*GENE therapy
*BLOOD proteins
*ANTITHROMBINS
Subjects
Details
- Language :
- English
- ISSN :
- 01429612
- Volume :
- 29
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 27363967
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2007.09.024