Copolymers of amine methacrylate with poly(ethylene glycol) as vectors forgene therapy

A series of structurally related copolymers of tertiary amine methacrylate with poly(ethylene glycol) (PEG) were investigated for their potential to s erve as vectors for gene therapy. The effects of copolymer structure on the complexation and transfection ability were assessed. The ability of the PE G-based copolymers and DMAEMA homopolymer to bind and condense DNA was conf irmed by gel electrophoresis. ethidium bromide displacement and transmissio n electron microscopy. The presence of PEG in the copolymers had a benefici al effect on their ability to bind to DNA. Colloidally stable complexes wer e obtained for all the PEG-copolymer systems as shown by uniformly discrete spherical images from transmission electron microscopy and approximate dia meters of 80-100 nm by dynamic light scattering studies. DMAEMA homopolymer , however, produced agglomerated particles, confirming the important role p layed by the PEG chains in producing compact stable DNA complexes. Assessme nt of the effect of ionic strength of the buffer on the complexation and di ssociation of the complexes indicated the importance of both electrostatic and non-electrostatic interactions in the polymer-DNA complexation. In vitr o transfection experiments showed that DMAEMA homopolymer gave the highest level of transfection comparable to a control poly-L-lysine (PLL) system. T he PEG-based copolymers gave reduced levels of transfection, most likely du e to the steric stabilization effect of a PEG corona. (C) 2001 Elsevier Sci ence B.V. All rights reserved.