These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Characterization of the transgene expression generated by branched and linear polyethylenimine-plasmid DNA nanoparticles in vitro and after intraperitoneal injection in vivo.
    Author: Intra J, Salem AK.
    Journal: J Control Release; 2008 Sep 10; 130(2):129-38. PubMed ID: 18538436.
    Abstract:
    Polyethylenimine (PEI) is a cationic polymer that has shown significant potential for delivering genes in vitro and in vivo. Mixing cationic PEI with negatively charged plasmid DNA (pDNA) results in the spontaneous electrostatic formation of stable nanoparticle complexes. The structure of PEI can be branched or linear. In this study, we show that branched PEI has a stronger electrostatic interaction with pDNA than linear PEI, which accounts for greater compaction, higher zeta potentials and smaller nanoparticle sizes at equivalent pDNA concentrations. For both linear and branched PEI, increasing the concentration of pDNA mixed in the same volume and at the same nitrogen to phosphate (N:P) ratio results in larger average particle sizes. Increasing the N:P ratio increases luciferase activity generated by branched PEI-pDNA nanoparticles and linear PEI-pDNA nanoparticles in HEK293, COS7 and HeLa cell lines. Increasing the N:P ratio at which branched PEI-pDNA nanoparticles are prepared also increases luciferase expression in HepG2 cells but does not increase luciferase expression generated by linear PEI-pDNA nanoparticles. In all of the cell lines, branched PEI-pDNA nanoparticles prepared at N:P ratios of 10 and above generated significantly higher luciferase activity than linear PEI-pDNA nanoparticles. Luciferase activity was highest in the HEK293 cells and luciferase expression in each of the cell lines followed the order of HEK293>COS7>HepG2>HeLa. Intraperitoneal (IP) injection of PEI-pDNA nanoparticles is attractive because it is simple, reproducible and often leads to a depot effect of nanoparticle complexes residing in the peritoneum. The IP route of administration avoids PEI-pDNA nanoparticle accumulation in the lung and the nanoparticles do not pass through the blood-brain barrier. In this study, using bioluminescent imaging (BLI), we show that changing the PEI structure and dose of the PEI-pDNA nanoparticles has a significant impact on the strength and duration of transgene expression after IP injection in vivo but increasing the N:P ratio does not. Increasing the dose and N:P ratio for all the PEI-pDNA nanoparticle formulations injected IP did not reduce mice survival and all mice remained in good health as determined by the Body Condition Scoring (BCS) technique.
    [Abstract] [Full Text] [Related] [New Search]