Targeting delivery of tocopherol and doxorubicin grafted-chitosan polymeric micelles for cancer therapy: In vitro and in vivo evaluation.

In this study, we report the development of a novel, redox-sensitive chitosan-based targeted drug delivery system, containing two drugs. We determined whether the synthesized polymeric micelles (HPTOC-DOX) were suitable as a drug carrier. The formation of HPTOC-DOX micelles was confirmed by (1)H NMR. HPTOC-DOX formed micelles of approximately 151.9-311.2nm in size in aqueous solution. Analysis of the drug release profile of HPTOC-DOX in different pH conditions (pH 5.2, 6.2, and 7.4) indicated that DOX was released from HPTOC-DOX micelles at acidic pH (5.2 or 6.2), while almost no DOX was released at pH 7.4. In vitro cell cytotoxicity and hemolysis assays indicated that HPTOC-DOX micelles safely deliver anti-cancer drugs and decrease the cytotoxicity of DOX. In vitro anti-cancer activity assays, confocal laser scanning microscopy analysis of SK-BR-3 cells, and in vivo anti-tumor activity in SK-BR-3-derived tumor-bearing mice were used to evaluate synergistic drug effects and the effect of the targeting peptide (anti-human epidermal growth factor receptor 2 [HER2] target peptide, epitope form; LTVSPWY) on receptor-mediated endocytosis.