PEGylation polyplex

Miyata K, Kakizawa Y, Nishiyama N, Yamasaki Y, Watanabe T, Kohara M, Kataoka K (2005) Freeze-dried formulations for in vivo gerre delivery of PEGylated polyplex micelles with disulfide crosslinked cores to the liver. J Corrtrol Release 109 15—23. 

PEGylation also appears to be a useful method of prolonging the blood circulation of polyplex after systemic administration, and PEGylated polyplex has resulted in gene transfer to a tumor without significant toxicity after intravenous injection into tumor-bearing mice.71... 

M. Oishi, K. Kataoka and Y. Nagasaki, pH-responsive threelayered PEGylated polyplex micelle based on a lactosylated ABC triblock copolymer as a targetable and endosome-disruptive non-viral gene vector. Bioconjugate Chem., 17,677-688 (2006). 

Fukushima, S., Miyata, K., Nishiyama, N., Kanayama, N., Yamasaki, Y. and Kataoka, K. (2005) PEGylated polyplex micelles from triblock catiomers with spatially ordered layering of condensed pDNA and buffering units for enhanced intracellular gene delivery. /. Am. Chem. Soc., 127,2810-2811. 

Several of these problems can be solved by polyplex modification with polyethylene glycol (PEG). PEGylation has been broadly explored for surface shielding ( stealthing ) of many liposomal and nanoparticulate carriers. In the case of cationic polymers, Plank et al. [62] demonstrated that complement activation can be reduced when the polymers are PEGylated. Such a modification can be... 

First clinical human gene therapy trials with polyplexes were performed using cancer vaccines based on autologous patient tumor cells. These were modified ex vivo with interleukin-2 pDNA. To obtain high level transfection rates of patient s primary tumor cells, Tf-PLL/pDNA polyplexes linked with inactivated endosomolytic adenovirus particles were applied [221]. Polymer-based in vivo human gene transfer studies were performed with PEGylated PLL polyplexes, delivering CFTR pDNA to the airway epithelium of cystic fibrosis patients [222],... 

Burke RS, Pun SH (2008) Extracellular barriers to in vivo PEI and PEGylated PEI polyplex-mediated gene delivery to the liver. Bioconjug Chem 19 693-704... 

Knorr V, Allmendinger L, Walker GF, Paintner FF, Wagner E (2007) An acetal-based PEGylation reagent for pH-sensitive shielding of DNA polyplexes. Bioconjug Chem 18 1218-1225... 

Rao GA, Tsai R, Roura D et al (2008) Evaluation of the transfection property of a peptide ligand for the fibroblast growth factor receptor as part of PEGylated polyethylenimine polyplex. J Drug Target 16 79-89... 

Fischer D, Osburg B, Petersen H, Kissel T, Bickel U. Effect of poly(ethylene imine) molecular weight and pegylation on organ distribution and pharmacokinetics of polyplexes with oligodeoxynucleotides in mice. Drug Metab Dispos 2004 32 983-992. 

Scheme 3.6 Formulation of polyplexes prepared from block- and graft-shaped PEGylated cationic polymers, synthesized by ATRP.

---