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Unprotonated PEI Protonated PEI
                   Unprotonated PEI                                                              Protonated PEI

PEI as antifection agent

Polyethylenimine (PEI) is a versatile vector for gene transfer into the cells. Its transfection efficiency has been well studied. It is a cationic polymer with higher cationic density than the other polycations like poly-L-lysine. PEI, when used as a gene delivery vector, complexes with DNA and provides a stable environment in respect to the degradation by the enzyme. It may provide a physical barrier to the enzyme by which enzyme could not reach DNA and/or the electrostatic interactions between the PEI and the enzyme prevent the enzyme to reach DNA. DNA coupled with PEI enters the cell through endocytosis, here, PEI protects DNA from lysosomal nucleases. The very low pH at the lysosomes, protonates PEI which results in the influx of chloride ions and leading to the osmotic swelling of the endosomes. At the very same time, due to protonation, PEI expands its polymeric network. Both process, the swelling of endosomes and the elongation of PEI leads to the bursting of the endosomes. This protects DNA to get degraded from the degradative lysosomal trafficking pathway and DNA gets introduced. This ability of PEI vectors to avoid the acidic lysosomes increases its transfection efficiency. At very low pH, we can expect the N-atoms getting protonated leading to the elongation of polymer and simultaneously, causing the endosomes to swell. The stability provided by the PEI leads it (DNA) to have a greater antifection efficiency than other polycations. 

PEI exists both in linear and branched form. The linear chains, has secondary nitrogens while the branched chain consists of primary, secondary and tertiary nitrogens. Linear PEI was first described to be prepared by alkaline hydrolysis of poly-N-formylethylenimine. It is also known that the linear PEI is very efficient non-viral gene antifection agent when compared with the branched counter part. PEI is effective at neutral and higher pH to get in complexation with DNA and at low pH it releases the DNA in the cell. Therefore structure of PEI and the competition between interactions of PEI with DNA and solvent molecules plays the crucial role in the mechanism of delivery of DNA inside the cell.

Solvation Dynamics of PEI

Solvation is a process where solute molecule interacts with the solvent leading to its stabilization. Solvent molecules diffuse into the porous structure of the polymer when it is exposed to the solvent. If the polymer is soluble in solvent, there is an attractive interactions between them while for the polymer segments the net interactions are repulsive. So, at this stage if the polymer is coiled it starts swelling and attains an equilibrium structure. Thus, understanding the polymer chain  dynamics, its equilibrium structure in the presence of solvent and the solvation structure are important. The solvation understanding is also vital for the biological perspectives as PEI is very efficient non-viral gene antifection agent.

PEI is a pH sensitive polymer which acts as proton sponge in acidic conditions. Despite many experimental and theoretical efforts, fundamental understanding of structure and dynamics of linear PEI chain in atomistic level at different protonation states in dilute solution remains topic of discussion. We have also studied the structural properties of PEI at different protonation states which are the representative of different pH using all atomistic molecular dynamic simulations.

For further details, please refer :

Chandan Kumar Choudhury , and Sudip Roy*, Structural and dynamical properties of Polyethylenimine in explicit water at different protonation states : Molecular Dynamics  

Soft Matter2013(7), 2269 - 2281

PEI - DOPC Interaction
The interaction of Polyethylenimine with lipid bilayer has been investigated. Its details has been documented at