Synthesis and evaluation of T85-LPEI copolymers for pDNA delivery

M.X. Wang
Carolinas Medical Center, US

Keywords: polymer, gene delivery, nanoparticles, non-viral vector


In this study, a series of low molecular weight PEI (LPEI) modified with Tween 85 were prepared by varying feed ratio and PEI size (Mw: 0.8k, 1.2k and 2.0k Da) for gene delivery. The Mws of the copolymers range from about 5,000 to 25,000 Da and PEI content from 6.8% to 21%. The copolymers condensed DNA efficiently with particles size below 200 nm at the weight ratio 5 of polymer/pDNA, and were stable in the presence of Serum or Heparin. The Tween 85-PEI copolymers led to a significant increase in the cellular uptake of pDNA with higher transfection efficiency in CHO and C2C12 cell lines, but without increase in toxicity compared with the parent LPEI. Transgene expression efficiency reached up to 6, 10 folds compared with PEI 25k at the same dose in vitro and in mdx mice in vivo, respectively (Fig. 1). There was no obvious muscle damage with the new copolymers. The results strongly indicate Tween 85 modified LPEI copolymers could be a potentially safe and effective carriers for gene/drug delivery.