Please use this identifier to cite or link to this item:
|Title:||New polyphosphoramidate with a spermidine side chain as a gene carrier|
|Keywords:||CNS gene delivery|
Non-viral gene delivery
|Citation:||Wang, J., Zhang, P.-C., Lu, H.-F., Ma, N., Wang, S., Mao, H.-Q., Leong, K.W. (2002-09-18). New polyphosphoramidate with a spermidine side chain as a gene carrier. Journal of Controlled Release 83 (1) : 157-168. ScholarBank@NUS Repository. https://doi.org/10.1016/S0168-3659(02)00180-3|
|Abstract:||A new cationic polymer (PPA-SP), polyphosphoramidate bearing spermidine side chain, was prepared as a non-viral vector for gene delivery. PPA-SP was synthesized from poly(1,2-propylene H-phosphonate) by the Atherton-Todd reaction. The weight average molecular weight of PPA-SP was 3.44×104 with a number average degree of polymerization of 90, as determined by GPC/LS/RI method. The average net positive charge per polymer chain was 102. PPA-SP was able to condense plasmid DNA efficiently and formed complexes at an N/P ratio (free amino groups in polymer to phosphate groups in DNA) of 2 and above, as determined by agarose gel electrophoresis. This new gene carrier offered significant protection to DNA against nuclease degradation at N/P ratios above 2, and showed lower cytotoxicity than PLL and PEI in cell culture. The LD50 of PPA-SP was 85 μg/ml in COS-7 cells, in contrast to 20 and 42 μg/ml for PLL and PEI, respectively. The complexes prepared in saline at N/P ratios of 5∼10 had an average size of 250 nm and zeta-potential of 26 mV. PPA-SP mediated efficient gene transfection in a number of cell lines, and the transfection protocol was optimized in HEK293 cells using a luciferase plasmid as a marker gene. Gene expression mediated by PPA-SP was greatly enhanced when chloroquine was used in conjunction at a concentration of 100 μM. Under the optimized condition, PPA-SP/DNA complexes yield a luciferase expression level closed to PEI/DNA complexes or Transfast mediated transfection. In a non-invasive CNS gene delivery model, PPA-SP/DNA complexes yielded comparable bcl-2 expression as PEI/DNA complexes in mouse brain stem following injection of the complexes in the tongue. © 2002 Elsevier Science B.V. All rights reserved.|
|Source Title:||Journal of Controlled Release|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on May 14, 2018
WEB OF SCIENCETM
checked on May 7, 2018
checked on May 18, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.