Gene transfer efficiency of high primary amine content, hydrophobic, alkyl-oligoamine derivatives of polyethylenimine.
 

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Gene transfer efficiency of high primary amine content, hydrophobic, alkyl-oligoamine derivatives of polyethylenimine.
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Gene transfer efficiency of high primary amine content, hydrophobic, alkyl-oligoamine derivatives of polyethylenimine.

Biomaterials. 2009 May 20;

Authors: Dehshahri A, Oskuee RK, Shier WT, Hatefi A, Ramezani M

In this study, a series of alkyl-oligoamine derivatives of low-toxicity 10kDa polyethylenimine (PEI) were synthesized to enhance the hydrophobicity of PEI while preserving most of its primary amine content. PEI was reacted with a series of omega-bromoalkylcarboxylic acids with different chain lengths (2-bromoacetic, 6-bromohexanoic, 10-bromodecanoic and 16-bromohexadecanoic acids) to modify hydrophobicity followed by coupling to various oligoamines (spermine, spermidine, ethylendiamine or diethylentriamine) to partially restore primary amine density. These modifications were designed to influence hydrophobic-hydrophilic balance as well as maintain the proton sponge effect in order to create an efficient vector with low toxicity. Ethidium bromide exclusion assays and dynamic light scattering studies showed that the modified PEIs could bind to plasmid DNA and form nanoparticles in the range of 100nm. The transfection efficiency of modified PEIs complexed with a luciferase reporter gene (pCMV-luc) in N2A murine neuroblastoma cells was increased to a level comparable to that of 25,000Da PEI. These results indicate that hydrophobic modification of low-toxicity PEI without reduction in primary amine content is an effective strategy for improving transfection efficiency of polycation-based non-viral vectors while maintaining low toxicity.

PMID: 19464054 [PubMed - as supplied by publisher]