Synthesis and antitumor activity of stearate-g-dextran micelles for intracellular doxorubicin delivery.

Stearate-g-dextran (Dex-SA) was synthesized via an esterification reaction between the carboxyl group of stearic acid (SA) and hydroxyl group of dextran (Dex). Dex-SA could self-assemble to form nanoscaled micelles in aqueous medium. The critical micelle concentration (CMC) depended on the molecular weight of Dex and the graft ratio of SA, which ranged from 0.01 to 0.08 mg mL(-1). Using doxorubicin (DOX) as a model drug, the drug encapsulation efficiency (EE%) using Dex-SA with 10 kDa molecular weight of Dex and 6.33% graft ratio of SA could reach up to 84%. In vitro DOX release from DOX-loaded Dex-SA micelles (Dex-SA/DOX) could be prolonged to 48 h, and adjusted by a different molecular weight of Dex, the graft ratio of SA, or the drug-loading content. Tumor cellular uptake test indicated that Dex-SA micelles had excellent internalization ability, which could deliver DOX into tumor cells. In vitro cytotoxicity tests demonstrated the Dex-SA/DOX micelles could maintain the cytotoxicity of commercial doxorubicin injection against drug-sensitive tumor cells. Moreover, Dex-SA/DOX micelles presented reversal activity against DOX-resistant cells. In vivo antitumor activity results showed that Dex-SA/DOX micelles treatments effectively suppressed the tumor growth and reduced the toxicity against animal body compared with commercial doxorubicin injection.