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Vivo Degradation Of Crosslinked Polyethylene Imine Synthesis And Applications

Posted on:2008-12-15Degree:MasterType:Thesis
Country:ChinaCandidate:H LiFull Text:PDF
GTID:2191360215998382Subject:Applied Chemistry
Abstract/Summary:PDF Full Text Request
The cationic polymers with high gene transfection efficiencies and little cytotoxicitywas synthesized. Due to its high gene transfection efficiency and easy availability,branched 25kDa PEI has become a benchmark to which other polymers, especially newlydesigned and synthesized materials, were often compared. However it is cytotoxic inmany cell lines. Smaller PEI. is usually non-cytotoxic but less efficient. In order toenhance the gene delivery efficiency and minimize cytotoxicity of PEI, one hundred andtwo of polymers were prepared by non-cytotoxic smaller PEI (branched 800Da or2000Da) reacting with different potentially biodegradable linkages that were found orsynthesized. However, some of these polymers were not soluble in water and thus theycould not be used in gene delivery. The polymers that is soluble in water were assessedwhen HEK293 cells was used as receptor cell and enhanced green fluorescent protein(EGFP) was used as gene reporter. In these polymers, we got one polymer with hightransfection efficiency (GFP positive ratio>88%). Then the molecular weight of thispolymer was measured and it is approximately 19000. And the transfection efficiency ofthis polymer was also investigated in other cell lines. Results showed that its transfectionefficiency exceeds 50% for these cells. For NIH3T3 cells, its transfection efficiency is1.5 times more efficient than that of Superfect and is 5 times more efficient than that of25kDa PEI respectively. In addition, cytotoxicity of this polymer was measured in 293T,3T3 cell lines. This polymer exhibits lower cytotoxicity than 25kDa PEI. Moreover, itstransfection efficiency is not affected by serum and is high in C57 mouse muscle. Allthese results show that this polymer is safe and efficient gene delivery vector in vitro andit is promising to be used in vivo.
Keywords/Search Tags:gene delivery, non-viral, polyethylenimine(PEI), degradable, cytotoxicity
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