A series of chemical modifications of chitosan were conducted by grafting a hydrophilic methoxy poly(ethylene glycol) (MPEG) and a target sugar molecule lactobionic acid (LA). The MPEG was grafted onto C6-OH position of chitosan, and the grafting degree was reduced for chitosan with high degree of depolymerization. The lactobionic acid was proposed to graft onto C2-NH2 position of chitosan. The LA grafting ratio was dependent on pegylation degree of chitosan, where the flexibility and shielding effect of MPEG hindered LA grafting onto chitosan. The lactobionic acid grafted pegylated chitosan, DADP-CS-(O-MPEG)-(N-LA), successfully provoked DNA condensation into nanoparticle complexes due to electrostatic compaction. The presence of MPEG on DADP-CS-(O-MPEG)-(N-LA) played an important role on preventing nanoparticle aggregation. (C) 2009 Elsevier Ltd. All rights reserved.