Polyethylenimine-based Formulations for Delivery of Oligonucleotides

Author(s): Fei Hao, Yuhuan Li, Jing Zhu, Jingyao Sun, Brian Marshall, Robert J. Lee, Lesheng Teng, Zhaogang Yang*, Jing Xie*

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 13 , 2019

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Polyethyleneimine (PEI) is well-known as a non-viral gene delivery vector, especially for oligonucleotide delivery. However, its clinical applications are significantly limited due to its high cationic charge, lack of specificity, and interaction with the proteins and nontarget cells in the biological fluids, resulting in high cytotoxicity, poor stability and low transfection efficiency for oligonucleotides transporting. It has been shown that the molecular weight (MW) of PEI, degree of branching, N/P ratio, buffer capacity, oligonucleotide structure, culture medium pH, serum, presence or absence of and method of preparation make a significant difference in the cytoxicity, stability, and transfection efficiency for the PEI-based oligonucleotides delivery systems. Ligands, hydrophobic, hydrophilic, and amphiphilic modification of PEI have been investigated to reduce the cytoxicity and improve the stability, the transfection efficiency, and therapeutic effect. Moreover, various intelligent modifications of PEI, such as pH-responsive (hydrazone bond) and redox sensitive linkers (disulfide bond) can control oligonucleotides release and have attracted much attention. In general, more efficient oligonucleotide delivery can be achieved by the introduction of modifications to PEI and by optimization of parameters of PEI or PEI-based formulations.

Keywords: Polyethylenimine, oligonucleotide delivery, drug, targeting, PEG modification, pH-sensitive linker, oligonucleotide delivery carrier.

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