ナノメディシンとナノテクノロジーのジャーナル

概要

Synthesis and Evaluation of Tween 85-LPEI Copolymers for Gene Transfection In vitro and In vivo

Mingxing Wang, Bo Wu, Jay D Tucker, Peijuan Lu, Sapana N Shah, Shante Wade and Qilong Lu

A series of cationic amphiphlic copolymers constructed from Tween 85 and low molecular weight (Mw) polyethyleneimene (LPEI) were prepared in ambient conditions and characterized. The Mws of these copolymers ranged from around 5,000 to 25,000 Da and PEI content from 8.25% to 20.91%. The new 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 introduction of Tween 85 led to a significant increase in the cellular uptake of complexes with higher transfection efficiency in CHO, C2C12, and HSkM cell lines, but without increase in toxicity compared with the parent LPEI. The best formulation for pDNA delivery produced transgene expression efficiency 5, 20-fold of PEI 25k in vitro and in mdx mice in vivo, respectively. There is no obvious muscle damage with these new copolymers at the injection sites. These results indicated that the presence of more hydrophobic groups within the new polymers is associated with higher transfection efficiency (TE), and the higher PEI content and Mw of polymers show higher TE with relatively higher toxicity. The Tween 85 modified LPEI could be a potentially safe and effective polymeric carriers for gene/drug delivery.