Copolymers of amine methacrylate with poly(ethylene glycol) as vectors for gene therapy.
A series of structurally related copolymers of tertiary amine methacrylate with poly(ethylene glycol) (PEG) were investigated for their potential to serve as vectors for gene therapy. The effects of copolymer structure on the complexation and transfection ability were assessed. The ability of the PEG-based copolymers and DMAEMA homopolymer to bind and condense DNA was confirmed by gel electrophoresis, ethidium bromide displacement and transmission electron microscopy. The presence of PEG in the copolymers had a beneficial effect on their ability to bind to DNA. Colloidally stable complexes were obtained for all the PEG-copolymer systems as shown by uniformly discrete spherical images from transmission electron microscopy and approximate diameters of 80-100 nm by dynamic light scattering studies. DMAEMA homopolymer, however, produced agglomerated particles, confirming the important role played by the PEG chains in producing compact stable DNA complexes. Assessment of the effect of ionic strength of the buffer on the complexation and dissociation of the complexes indicated the importance of both electrostatic and non-electrostatic interactions in the polymer-DNA complexation. In vitro transfection experiments showed that DMAEMA homopolymer gave the highest level of transfection comparable to a control poly-L-lysine (PLL) system. The PEG-based copolymers gave reduced levels of transfection, most likely due to the steric stabilization effect of a PEG corona.
Rungsardthong
U
U
School of Pharmaceutical Sciences, University of Nottingham, University Park, NG7 2RD, Nottingham, UK.
Deshpande
M
M
Bailey
L
L
Vamvakaki
M
M
Armes
S P
SP
Garnett
M C
MC
Stolnik
S
S
D004247:DNA / Q000008:administration & dosage* / Q000378:metabolism; D004355:Drug Stability; D004587:Electrophoresis, Agar Gel; D015316:Genetic Therapy; D005822:Genetic Vectors; D008689:Methacrylates / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011199:Potentiometry; D012542:Scattering, Radiation; D014162:Transfection
D008689:Methacrylates; D011092:Polyethylene Glycols; D004247:DNA; C049840:2-(dimethylamino)ethyl methacrylate