Polyethylenimine endosomal escape

Another possible method of endosome escape is the proton-sponge hypothesis [74]. Non viral DNA vectors that are able to accept protons at physiological pHs, such as polyethylenimine (PEI), act as a buffering agent within endosomes. As a result, more protons are pumped into the endosome, accompanied by an influx of chloride ions (to maintain the appropriate membrane potential) and water (due to osmotic pressure), which may lead to endosome rupture. 

Polyethylenimine (PEI) is the most outstanding example for synthetic cationic polymers because of its wide range of applications. It can be synthesized in linear (LPEI) as well as in branched (BPEI) structures. LPEI possesses primary and secondary amino groups, whereas BPEI also features tertiary amino groups. BPEI usually has a ratio of primary to secondary to tertiary amino functionalities of 1 2 1 and up to 25% of these amino groups are protonated under physiological conditions. Such buffer capability can also be utilized for endosomal escape mechanisms. The amino... 

In the literature, chitosan nanoparticles have been shown to neutralize the surface charge of liver cancer eells, deerease the membrane potential of mitochondria and indicate lipid peroxidation thus they eause neerotic death. Chitosan nanoparticles form either polyplexes or eneapsulate aetive molecules in their nanoparticle matrix.However, chitosan nanoparticles have lower transfection efficiency than synthetic cationic polymers sueh as polyethylenimine because of their lower endosomal escape. ... 

Cationic polymers [11-13], such as polyethylenimine (PEI) and poly-lysine are linear or branched polymers with a good endosomal escape. Their transfection efficiency mainly depends on molecular weight [14—16]. 

Polyethylenimine (PEI) (1), which has been shown to transfer genes both in vitro and in vivo. It has a number of chemical/structural properties which are quite different fiom cationic liposomes and may be advantageous for gene delivery. The size of PEI/DNA complexes is very small (<100 nm potentially allowing for better distribution. It also appears to be efficient at endosomal escape, thus reducing DNA degradation. 

An interesting system for the delivery of proteins into the cytosol was recently reported. The system was based on a branched polyethylenimine (PEI) which was modified by introducing thiol functions and subsequently polymerized (oxidized) with the formation of disulfide bonds. This polymer was able to complex bovine serum albumin (BSA), an anionic protein. The PEC formed showed negligible cytotoxicity and the complexation did not result in structural damage of the protein. The complexes could be internalized into the endosomes and lysosomes and could escape from them. 

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