Polyethylenimine/arabinogalactan conjugate as a hepatocyte specific gene carrier

Polyethylenimine/arabinogalactan (PEI-AG) conjugates were prepared as a hepatocyte-specific DNA carrier. The conjugate were successfully prepared by reductive amination reaction between the reductive end of arabinogalactan (AG) and amino groups of polyethylenimine using NaBH3CN as a catalyst, regardless of the highly branched structure of AG. By changing the AG content in the feed, PEI-AG conjugates containing controlled AG contents were obtained. The conjugates, with AG contents ranging from 47 to 88 weight%, form complexes with plasmid DNA at the same polyethylenimine/DNA ratio. This indicates that AG dig not severely affect the interaction between DNA and polyethylenimine moiety in the conjugates. Small DNA complexes (100-200 nm) were formed when plasmid DNA was mixed with PEI-AG conjugates. The complexes maintained dispersive stability in phosphate-buffered saline over a month, indicating that AG moieties contribute to the solubility of the complexes. The surface positive charge of polyethylenimine/DNA complexes decreased with an increase in AG content. The transfection activity of polyethylenimine/DNA complexes toward HeLa or 3T3 cells (asialoglycoprotein receptors negative) was strongly reduced by AG conjugation whereas that towards murine primary hepatocytes (asialoglycoprotein receptors positive) was preserved. The results indicated that PEI-AG conjugates could avoid the non-specific interaction with cells while maintaining the high-level transfection efficiency by asialoglycoprotein receptor-mediated gene expression.