Targeting of stabilized plasmid lipid particles to hepatocytes in vivo by means of coupled lactoferrinWeeke-Klimp, A. H., Bartsch, M., Morselt, H. W. M., Van Veen-Hof, I., Meijer, D. K. F., Scherphof, G. L. & Kamps, J. A. A. M., 2007, In : Journal of Drug Targeting. 15, 9, p. 585-594 10 p.
Research output: Contribution to journal › Article › Academic › peer-review
For non-viral gene delivery we prepared stabilized plasmid lipid particles (SPLPs), to which lactoferrin (LF) was coupled as a hepatocyte specific targeting ligand. LF-SPLPs and untargeted SPLPs labeled with [H-3]cholesteryloleyl-ether were injected into rats. About 87% of the LF-SPLPs were eliminated from the blood within 5 min, while 80% of untargeted SPLPs were still circulating after 2 h. Fifty-two percent of the LF-SPLPs were taken up by hepatocytes, while non-parenchymal liver cells accounted for 16% of the uptake. Despite the efficient targeting of LF-SPLPs to hepatocytes and their capacity to transfect HepG2 and COS-7 cells in vitro, expression of a reporter gene was not detected in vivo. Overall, covalent coupling of LF to SPLPs leads to massive delivery in hepatocytes after systemic administration. However, these LF-SPLPs are not able to transfect these cells in vivo.
|Number of pages||10|
|Journal||Journal of Drug Targeting|
|Publication status||Published - 2007|
- stabilized plasmid lipid particles, lactoferrin, gene targeting, hepatocytes, non-parenchymal liver cells, GENE-TRANSFER, RAT-LIVER, ENDOTHELIAL-CELLS, KUPFFER CELLS, BINDING, DNA, ACTIVATION, LIPOSOMES, DELIVERY, PROTEIN