The aim of this study was to evaluate the potential of carboxymethyl chitosan (CM-chitosan) nanoparticles as carriers for the anticancer drug, doxorubicin (DOX). Different kinds of CM-chitosan with various molecular weight (MW) and degree Of Substitution (DS) were employed to prepare nanoparticles through ionical gelification with calcium ions. Factors affecting nanoparticles formation in relation to MW and DS of CM-chitosan were discussed. By the way of dynamic light scattering (DLS), TEM, and atomic force microscopy (AIM), nanoparticles were shown to be around 200-300 nm and in a narrow distribution. FTIR revealed strong electrostatic interactions between carboxyl groups of CM-chitosan and calcium ions. DOX delivery was affected by the molecular structure of CM-chitosan. Increasing MWs of CM-chitosan from 4.50 to 38.9 kDa, DOX entrapment efficiency was enhanced from 10 to 40% and higher DS slightly improved the load of DOX. In vitro release studies showed an initial burst followed by an extended slow release. The DOX release rate was hindered by CM-chitosan with high MW and DS. These preliminary studies showed the feasibility of CM-chitosan nanoparticles to entrap DOX and the potential to deliver it as controlled release nanoparticles. (c) 2006 Wiley Periodicals, Inc.