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Synthesis of PEGylated cationic curdlan derivatives with enhanced biocompatibility.

Authors :
Muqier, Muqier
Xiao, Hai
Yu, Xiang
Li, Yifeng
Bao, Mingming
Bao, Qingming
Han, Shuqin
Baigude, Huricha
Source :
Journal of Biomaterials Science -- Polymer Edition; Mar2022, Vol. 33 Issue 4, p465-480, 16p
Publication Year :
2022

Abstract

Cationic polysaccharides have shown excellent ability of nucleic acids delivery. However, cationic curdlan derivatives with high degree of amination cause damage to the cell membrane and induce considerable cytotoxicity, limiting their in vivo application. Herein, we synthesized PEGylated 6-amino-6-deoxy-curdlan derivatives containing cleavable disulfide bonds. The resulting polymers (denote 6AC-2S PEGx) not only showed high affinity to siRNA but also exhibited significantly decreased cytotoxicity and hemolysis effect, while showing remarkable in vitro transfection efficiency. In vivo study demonstrated that 6AC-2S PEG40, which had a lower LD50 value than that of 6AC-100, did not cause liver damage, as the i.v. injection of 6AC-2S PEG40 to mouse did not increase serum level of ALT/AST. Furthermore, tissue distribution results showed that 6AC-2S PEG40 successfully delivered siRNA to liver, lung and spleen. Collectively, our data confirmed that PEGylation can increase the biocompatibility of cationic curdlan derivatives, which is a promising carrier for nucleic acid therapeutics. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09205063
Volume :
33
Issue :
4
Database :
Complementary Index
Journal :
Journal of Biomaterials Science -- Polymer Edition
Publication Type :
Academic Journal
Accession number :
155403094
Full Text :
https://doi.org/10.1080/09205063.2021.1992589