Synthesis of lactobionic acid-grafted-pegylated-chitosan with enhanced HepG2 cells transfection

The aim of this study was to develop a functional nanoparticulate carrier with an enhanced transfection in asialoglycoprotein receptor overexpressed HepG2 cells. A series of chemical modifications of chitosan were conducted by grafting a hydrophilic methoxy poly(ethylene glycol) (MPEG) and a receptor ligand, lactobionic acid (LA). The pegylation efficiency of deacetylated-depolymerized-chitosan (DADP-CS) was 26% (w/w). Increase in feed molar ratio of lactobionic acid from 0.25 to 0.5 increased LA grafting degree of lactobionic acid-grafted-pegylated-chitosan (DADP-CS-(O-MPEG)-(N-LA)) from 10% to 28%. Plasmid DNA was more compacted by DADP-CS-(O-MPEG)-(N-LA) than by pegylated-chitosan (DADP-CS-(O-MPEG)) in terms of smaller particle size of DADP-CS-(O-MPEG)-(N-LA)/DNA nanoparticle complex. The bearing of receptor ligand of DADP-CS-(O-MPEG)-(N-LA) (45.3%) showed better transfection efficiency than ligand-free DADP-CS-(O-MPEG) (19.8%) in asialoglycoprotein receptor overexpressed HepG2 cells.