title: Targeting delivery of tocopherol and doxorubicin grafted-chitosan polymeric micelles for cancer therapy: In vitro and in vivo evaluation.
abstract: 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.
authors.affiliation: Department of Polymer Science and Engineering, College of Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Jeollanam-do, Republic of Korea.
authors.forename: Joung-Pyo
authors.initials: JP
authors.lastname: Nam
authors.affiliation: Department of Polymer Science and Engineering, College of Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Jeollanam-do, Republic of Korea.
authors.forename: Kyeong-Jae
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Joung-Woo
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
authors.affiliation: Department of Polymer Science and Engineering, College of Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Jeollanam-do, Republic of Korea. Electronic address: jwnah@sunchon.ac.kr.
authors.forename: Jae-Woon
authors.initials: JW
authors.lastname: Nah
mesh_terms: D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy*; D011108:Polymers / Q000737:chemistry*; D024505:Tocopherols / Q000008:administration & dosage*
chemical_list: D008823:Micelles; D011108:Polymers; D004317:Doxorubicin; D048271:Chitosan; D024505:Tocopherols
keywords: Chitosan; Doxorubicin; Targeted delivery; pH-sensitive