Intracellular delivery of VEGF165 encoding gene therapeutic using trifunctional copolymers of ethylene oxide and propylene oxide

Abstract

© 2015 Elsevier Ltd. New type of copolymers of propylene oxide and ethylene oxide was assessed for promoting delivery of plasmid DNA based gene therapeutics. Lipid-like trifunctional copolymers (TFCs), with both random or diblock structures and relatively low hydrophilic-lipophilic balance, were studied and compared with linear Pluronic™ L61. Structure-dependent relationships for micelle-forming, cytotoxic and hemolytic properties of these copolymers were revealed. The TFC with the mean number of propylene oxide and ethylene oxide units of 83.5 and 24.2, respectively, exhibited relatively low adverse effects in vitro. The latter TFC interacted with plasmid DNA-polyethyleneimine complexes and improved their intracellular delivery. Furthermore, this TFC efficiently promoted the transfection of dermal fibroblasts with VEGF165-encoding Neovasculgen® plasmid DNA, which has been clinically used for the therapeutic angiogenesis. Our findings demonstrated for the first time that TFCs are promising for the polymer-mediated delivery of gene therapeutics.