PH Sensitive Vinyl Copolymers as Vectors for Gene Therapy

Abstract

A series of pH-sensitive vinyl (co)polymers was synthesised to investigate whether the buffering capacity is a crucial factor in determining the transfection efficiency of synthetic vectors in gene therapy. The polymers containing side groups with different pKa were prepared by radical polymerization. All cationic polymers were able to condense DNA, yielding rather small and homogeneous particles, as determined by dynamic light scattering. The effect of pH, temperature and serum albumin on complex formation was also investigated. The results from the titration studies showed that copolymers of (2-dimethylaminoethyl) methacrylate and 4-methyl-5-imidazoyl methyl methacrylate or methacrylic acid have a buffering effect over a broader pH range compared to poly(2-dimethylaminoethyl methacrylate). Introduction of N-(2-hydroxyethyl) nicotinamide methacrylate had no significant effect on the buffering range.