Self-assembled nanoparticle drug delivery systems from galactosylated polysaccharide-doxorubicin conjugate loaded doxorubicin.

Xyloglucan was grafted with the doxorubicin (DOX) and galactosamine, a terminal moiety that can be used to target polymeric conjugates to liver hepatocytes. The content of the DOX was over 5% (wt) in the conjugate. The polymeric drug assisted to form nanoparticle drug delivery systems (nanoDDSs) with an average size of 142 nm in diameter when combined with an excess amount of deprotonated doxorubicin in an aqueous phase. A loading content of doxorubicin is as high as 23.8% in the nanoDDS. In an in vitro cytotoxicity experiment, the novel nanoDDS has similar cytotoxicity as free DOX against HepG2 cells. In contrast, for the incubation with HeLa cells of the novel nanoDDS, there was no significant cytotoxicity change. In a human tumor xenograft nude mouse model, the novel nanoDDS generated higher therapeutic effect than non-targeted doxorubicin nanoparticles or free doxorubicin. Together, these results suggest that novel nanoDDS, which has improved transfection efficiency and hepatocyte specificity, may be useful for tumor therapy. 2009 Elsevier B.V. All rights reserved.