Enhanced Coil Expansion and Intrapolymer Complex Formation of Linear Poly(methacrylic acid) Containing Poly(ethylene glycol) Grafts†

2004 ◽  
Vol 37 (7) ◽  
pp. 2603-2612 ◽  
Author(s):  
Garrett D. Poe ◽  
William L. Jarrett ◽  
Charles W. Scales ◽  
Charles L. McCormick
Keyword(s):  
Complex Formation ◽  
Ethylene Glycol ◽  
Methacrylic Acid ◽  
Poly Ethylene Glycol ◽  
Linear Poly ◽  
Poly Ethylene

scholarly journals Bottlebrush-architectured poly(ethylene glycol) as an efficient vector for RNA interference in vivo

2019 ◽  
Vol 5 (2) ◽  
pp. eaav9322 ◽  
Author(s):  
Dali Wang ◽  
Jiaqi Lin ◽  
Fei Jia ◽  
Xuyu Tan ◽  
Yuyan Wang ◽  
...  
Keyword(s):  
Rna Interference ◽  
Ethylene Glycol ◽  
Target Genes ◽  
Area Under The Curve ◽  
Fold Increase ◽  
Small Interfering Rnas ◽  
Poly Ethylene Glycol ◽  
Linear Poly ◽  
Poly Ethylene

Nonhepatic delivery of small interfering RNAs (siRNAs) remains a challenge for development of RNA interference–based therapeutics. We report a noncationic vector wherein linear poly(ethylene glycol) (PEG), a polymer generally considered as inert and safe biologically but ineffective as a vector, is transformed into a bottlebrush architecture. This topology provides covalently embedded siRNA with augmented nuclease stability and cellular uptake. Consisting almost entirely of PEG and siRNA, the conjugates exhibit a ~25-fold increase in blood elimination half-life and a ~19-fold increase in the area under the curve compared with unmodified siRNA. The improved pharmacokinetics results in greater tumor uptake and diminished liver capture. Despite the structural simplicity these conjugates efficiently knock down target genes in vivo without apparent toxic and immunogenic reactions. Given the benign biological nature of PEG and its widespread precedence in biopharmaceuticals, we anticipate the brush polymer–based technology to have a significant impact on siRNA therapeutics.

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