title: Improved anti-melanoma effect of a transdermal mitoxantrone ethosome gel.
abstract: Melanomas are malignant tumors characterized by early metastasis, rapid development, poor prognosis and high mortality. A highly effective and convenient method is necessary for long-term treatment of melanomas. Mitoxantrone (MTO) was topically applied for melanoma therapy using an MTO ethosome gel. Firstly, an ethosome was prepared from MTO, phospholipids, ethanol and water followed by addition of hydroxypropyl methylcellulose to obtain an ethosome gel. The ethosome was characterized. The cytotoxicity on B16 melanoma cells was evaluated on an electrical cell-substrate impedance sensing system with a novel modified chip. In vivo anti-melanoma effect of the ethosome gel was explored. Immunohistochemical and flow cytometric investigations were done. The MTO ethosomes had the size of 78nm and the zeta potential of -55mV. The ethosomes were flexible vesicles and showed much higher in vitro permeability across the rat skin than MTO aqueous solutions. The ethosomes had significant cytotoxicity and higher in vivo anti-melanoma effect than MTO solutions. The calreticulin membrane translocation of B16 cells was improved by the MTO ethosomes and the cell uptake of MTO was confirmed. The MTO ethosome gel is a promising transdermal delivery system for melanoma therapy with the advantages of non-invasion and no significant side effects.
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China; Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China; Anhui Medical University, Hefei 230001, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Du
authors.affiliation: Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China; Anhui Medical University, Hefei 230001, China.
authors.forename: Guiying
authors.initials: G
authors.lastname: Fu
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China; Anhui Medical University, Hefei 230001, China. Electronic address: jinyg@bmi.ac.cn.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D005782:Gels; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005782:Gels; D008942:Mitoxantrone
keywords: Electrical cell-substrate impedance sensing system; Ethosome; Melanoma; Mitoxantrone; Transdermal