Carboxylated Hydroxyethyl Starch: A novel Polysaccharide for the Delivery of Doxorubicin

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Abstract

Hydroxyethyl starch (HES) was interacted with succinic anhydride affording a carboxylated derivative which has proved to be a promising polymeric drug delivery system. Specifically, this polymer is conveniently prepared, is biodegradable, non-immunogenic, and can encapsulate doxorubicin due to the protonation of the primary amino group of doxorubicin by the carboxylic group located on the branched scaffold of the polysaccharide. In addition, due to the polyhydroxylated character of the polysaccharide, the latter can act as a protective coating in an analogous manner to the PEG-chains ensuring prolonged circulationin vivo. In vitroexperiments showed controlled release of doxorubicin to the nuclei of DU145 prostate cancer cells when the anticancer drug is incorporated in the carboxylated hydroxyethyl starch.

Carboxylated hydroxyethyl starch was prepared and investigated as a potential drug delivery system of doxorubicin, DOX. Employing DU145 human prostate cancer cells, the well-established localization of free DOX inside nuclei was not observed. On the contrary, when the drug was encapsulated in this carrier, it was preferentially localized in the cytosol, as shown in the figure. Significant cytotoxicity was only observed after ˜48 h due to slow controlled release of DOX which is electrostatically attached to the polysaccharide scaffold.

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