Polyethylenimine/arabinogalactan conjugate as a hepatocyte specific gene carrier

Polyethylenimine/arabinogalactan (PEI-AG) conjugates were prepared as a hep atocyte-specific DNA carrier. The conjugate were successfully prepared by r eductive amination reaction between the reductive end of arabinogalactan (A G) and amino groups of polyethylenimine using NaBH3CN as a catalyst, regard less 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 comp lexes with plasmid DNA at the same polyethylenimine/DNA ratio. This indicat es that AG dig not severely affect the interaction between DNA and polyethy lenimine moiety in the conjugates. Small DNA complexes (100-200 nm) were fo rmed when plasmid DNA was mixed with PEI-AG conjugates. The complexes maint ained dispersive stability in phosphate-buffered saline over a month, indic ating that AG moieties contribute to the solubility of the complexes. The s urface positive charge of polyethylenimine/DNA complexes decreased with an increase in AG content. The transfection activity of polyethylenimine/DNA c omplexes toward HeLa or 3T3 cells (asialoglycoprotein receptors negative) w as strongly reduced by AG conjugation whereas that towards murine primary h epatocytes (asialoglycoprotein receptors positive) was preserved. The resul ts indicated that PEI-AG conjugates could avoid the non-specific interactio n with cells while maintaining the high-level transfection efficiency by as ialoglycoprotein receptor-mediated gene expression.