A folate-poly(ethylene glycol) conjugate capable of covalent coupling to primary amines present at the surface of polyplexes was developed. Coating of poly(dimethylaminomethyl methacrylate (pDMAEMA)-based polyplexes with this folate-pEG conjugate led to a sharp decrease of the zeta-potential, and a small increase in particle size. The size of the particles in isotonic medium did not change markedly in time demonstrating that rather stable particles were formed. The in vitro cellular toxicity of the pEGylated polyplexes with and without folate ligands was lowered considerably compared to uncoated polyplexes. The toxicity observed for the targeted pEGylated polyplexes was slightly higher than that of corresponding untargeted polyplexes, which might indicate an increased cellular association of targeted polyplexes. Transfection of OVCAR-3 cells in vitro was markedly increased compared to untargeted pEGylated polyplexes, suggesting targeted gene delivery.
Copyright 2002 Elsevier Science B.V.