TY - JOUR
T1 - Polyethylenimine-based formulations for delivery of oligonucleotides
AU - Hao, Fei
AU - Li, Yuhuan
AU - Zhu, Jing
AU - Sun, Jingyao
AU - Marshall, Brian
AU - Lee, Robert J.
AU - Teng, Lesheng
AU - Yang, Zhaogang
AU - Xie, Jing
N1 - Publisher Copyright:
© 2019 Bentham Science Publishers.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Drug
KW - Oligonucleotide delivery
KW - Oligonucleotide delivery carrier
KW - PEG modification
KW - PH-sensitive linker
KW - Polyethylenimine
KW - Targeting
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U2 - 10.2174/0929867325666181031094759
DO - 10.2174/0929867325666181031094759
M3 - Article
C2 - 30378483
AN - SCOPUS:85070992856
SN - 0929-8673
VL - 26
SP - 2264
EP - 2284
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
IS - 13
ER -