Yu Xiang, Du Lina, Li Yu, Fu Guiying, Jin Yiguang
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.
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Biomed Pharmacother. 2015 Jul;73:6-11. doi: 10.1016/j.biopha.2015.05.002. Epub 2015 May 20.
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.
黑色素瘤是一种恶性肿瘤，具有早期转移、发展迅速、预后不良和死亡率高的特点。长期治疗黑色素瘤需要一种高效便捷的方法。采用米托蒽醌（MTO）脂质体凝胶局部应用于黑色素瘤治疗。首先，由MTO、磷脂、乙醇和水制备脂质体，随后加入羟丙基甲基纤维素得到脂质体凝胶。对脂质体进行了表征。在具有新型改良芯片的细胞-基质阻抗传感系统上评估其对B16黑色素瘤细胞的细胞毒性。探讨了脂质体凝胶的体内抗黑色素瘤作用。进行了免疫组织化学和流式细胞术研究。MTO脂质体大小为78nm，ζ电位为-55mV。脂质体是柔性囊泡，在大鼠皮肤上的体外渗透率比MTO水溶液高得多。脂质体具有显著的细胞毒性，体内抗黑色素瘤作用比MTO溶液更强。MTO脂质体改善了B16细胞的钙网蛋白膜转位，并证实了MTO的细胞摄取。MTO脂质体凝胶是一种有前景的用于黑色素瘤治疗的透皮给药系统，具有无创和无明显副作用的优点。
