Polyethylenimine-based formulations for delivery of oligonucleotides.

Hao F, Li Y, Zhu J, Sun J, Marshall B, Lee RJ, Teng L, Yang Z, Xie J
Curr Med Chem in press 10/30/2018


Polyethylenimine (PEI) is well-known as the non-viral gene delivery vector, especially for the oligonucleotides delivery. However, its clinical applications are significantly limited due to its high cationic charge, low cell recognition, and interaction with the proteins and non-target cells in the biological fluids, resulting in high cytotoxicity, poor stability and low transfection efficiency for oligonucleotides transporting. Many researchers have concluded that the molecular weight (MW) of PEI, degree of branched or linear structure, N/P ratio, buffer capacity, oligonucleotides structure, culture medium pH, serum, and different types of PEI-based particles including preparation methods make a great difference in the cell toxicity, stability, transfection efficiency for the PEI-based oligonucleotides delivery systems. Ligands, small molecules, peptides targeting conjugation, hydrophobic, hydrophilic, and amphiphilic modification of PEI are also deeply investigated to reduce the cell toxicity and improve the stability, transfection efficiency, and therapeutic effect. Moreover, various intelligent modifications of PEI such as pH responsive bond (hydrazone bond) and redox sensitive bond (disulfide bond) could accurately control oligonucleotides release and have attracted attention for efficient oligonucleotides delivery. In general, the efficient oligonucleotides delivery could be achieved by the different modifications of PEI with optimized parameters of PEI or PEI-based formulations.

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