PEGylated chitosan-based polymer micelle as an intracellular delivery carrier for anti-tumor targeting therapy

Stearic acid-grafted chitosan oligosaccharide (CSO-SA) micelles presented a potential candidate for intracellular drug delivery carrier due to its special spatial structure. In this article, CSO-SA was further modified by polyethylene glycol (PEG). The physicochemical properties of PEGylated CSO-SA (PEG-CSO-SA) micelles were characterized. After PEGylation, the critical micelle concentration (CMC) of PEG-CSO-SA had no significant change; the micelle size increased; and the zeta potential decreased. The cellular uptake of CSO-SA micelles before and after PEGylation in macrophage RAW264.7, immortalized rat liver cells BRL-3A and human liver tumor cells HepG2 was Studied. About 58.4 +/- 0.63% of CSO-SA micelles were uptaked by RAW264.7 in 24 h, however, only 17.7 +/- 0.94% of PEG-CSO-SA micelles were internalized into RAW264.7 after the CSO-SA was modified with PEG in five molar times. Meanwhile, there were no changes in the uptake after PECylation of CSO-SA in BRL-3A and HepG2. Using mitomycin C as a model drug, the in vitro and-tumor activities of the drug loaded in the micelles were investigated. The 50% cellular growth inhibition (IC50) of the drug decreased from 1.97 +/- 0.2 to 0.13 +/- 0.02 mu g/mL after mitomycin C was loaded into CSO-SA micelles, and the IC50 value of the drug had no obvious change when the CSO-SA was modified by PEG. (C) 2008 Elsevier B.V. All rights reserved.