title: Melanoma therapy with transdermal mitoxantrone cubic phases.
abstract: BACKGROUND
  Melanoma therapy absorbs attention because of the high morbidity and mortality. However, currently systematic administrations could take little therapeutic efficiency and severe side effects.
  
  
  OBJECTIVE
  An effective transdermal formulation for the convenient melanoma therapy was found and evaluated.
  
  
  METHODS
  A mitoxantrone (MTO) cubic phase was prepared with glyceryl monooleate, ethanol and water. The permeation, cytotoxicity, in vivo anti-melanoma effect of the MTO cubic phases were evaluated. The anti-cancer mechanism of the MTO cubic phases was explored according to the immunohistochemistry and flow cytometry.
  
  
  CONCLUSIONS
  The isotropic structure of MTO cubic phases was identified. The transdermal permeability of MTO was greatly improved by the cubic phase compared to that of the MTO solution. The MTO cubic phases showed the high cytotoxicity in B16 melanoma cells evidenced by a modified electrical cell-substrate impedance sensing system. High anti-melanoma effect of the MTO cubic phases was confirmed according to the tumor volume changes and tumor weight. The tumor inhibitory rate of the MTO cubic phases was 68.44%. The calreticulin expression of B16 cells was improved by the MTO cubic phases, and the improved cell uptake of MTO was confirmed by the flow cytometry.
  
  
  CONCLUSIONS
  The MTO cubic phase is a promising topical delivery system for melanoma therapy with the advantages of non-invasion and no severe side effects.
authors.affiliation: a Department of Graduates , Anhui Medical University , Hefei , P.R. China .|b Department of Pharmaceutical Sciences , Beijing Institute of Radiation Medicine , Beijing , P.R. China , and.|c Affiliated Hospital of Academy of Military Medical Sciences , Beijing , P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.affiliation: b Department of Pharmaceutical Sciences , Beijing Institute of Radiation Medicine , Beijing , P.R. China , and.
authors.forename: Lina
authors.initials: L
authors.lastname: Du
authors.affiliation: a Department of Graduates , Anhui Medical University , Hefei , P.R. China .|b Department of Pharmaceutical Sciences , Beijing Institute of Radiation Medicine , Beijing , P.R. China , and.
authors.forename: Lifei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: b Department of Pharmaceutical Sciences , Beijing Institute of Radiation Medicine , Beijing , P.R. China , and.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: b Department of Pharmaceutical Sciences , Beijing Institute of Radiation Medicine , Beijing , P.R. China , and.
authors.forename: Baolei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: a Department of Graduates , Anhui Medical University , Hefei , P.R. China .|c Affiliated Hospital of Academy of Military Medical Sciences , Beijing , P.R. China.
authors.forename: Guiying
authors.initials: G
authors.lastname: Fu
authors.affiliation: a Department of Graduates , Anhui Medical University , Hefei , P.R. China .|b Department of Pharmaceutical Sciences , Beijing Institute of Radiation Medicine , Beijing , P.R. China , and.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000279:Administration, Cutaneous; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D005989:Glycerides / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D010539:Permeability; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D005989:Glycerides; D008942:Mitoxantrone; C005953:monoolein
keywords: Calreticulin; electrical cell–substrate impedance sensing system; flow cytometry; glyceryl monooleate; permeability