Abstract Melanoma is the most deadly and life-threatening form of skin cancer with progressively higher rates of incidence worldwide. The objective of the present investigation is to develop and to statistically optimize and characterize curcumin (CUR) loaded ethosomes for treatment of melanoma. A two factor, three level (32) factorial design approach was employed for the optimization of ethosomes. The prepared ethosomes were evaluated for size, zeta potential, entrapment efficiency, in vitro skin permeation and deposition ability. The optimized ethosomal formulation was evaluated for in vitro cytotoxicity and cellular uptake studies using A375 human melanoma cells. The optimized formulation has imperfect round shaped unilamellar structures with a mean vesicle size of 247 ± 5.25 nm and an entrapment efficiency of 92.24 ± 0.20%. The in vitro skin permeation studies proved the superiority of ethosomes over the traditional liposomes in terms of the amount of drug permeated and deposited in skin layers. Fluorescence microscopy showed the enhanced penetration of ethosomes into the deeper layers of the skin. In vitro cytotoxicity and cellular uptake studies revealed that curcumin ethosomes have significantly improved cytotoxicity and cellular uptake in A375 human melanoma cell lines. The colony formation assay results showed that curcumin ethosomes have a superior antiproliferative effect as they effectively inhibit the clonogenic ability of A375 cells. The flow cytometry results indicate that curcumin ethosomes induce cell death in A375 cells by apoptosis mechanism. The present study provides a strong rationale and motivation for further investigation of newly developed curcumin ethosomes as a potential therapeutic strategy for melanoma treatment.

中文翻译：

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用于皮肤癌递送的基于因子设计的姜黄素 ethosomal 纳米载体：体外评估

摘要 黑色素瘤是最致命和威胁生命的皮肤癌，在全球范围内的发病率越来越高。本研究的目的是开发和统计优化和表征加载姜黄素 (CUR) 的 ethosome，用于治疗黑色素瘤。使用二因素、三水平 (32) 因子设计方法来优化 Ethosomes。对制备的 ethosome 进行了大小、zeta 电位、包埋效率、体外皮肤渗透和沉积能力的评估。使用 A375 人黑色素瘤细胞对优化的 ethosomal 配方进行了体外细胞毒性和细胞摄取研究的评估。优化后的配方具有不完美的圆形单层结构，平均囊泡尺寸为 247 ± 5.25 nm，截留效率为 92.24 ± 0.20%。体外皮肤渗透研究证明，就渗透和沉积在皮肤层中的药物量而言，ethosomes 优于传统脂质体。荧光显微镜显示，ethosomes 渗透到皮肤更深层的能力增强。体外细胞毒性和细胞摄取研究表明，姜黄素 Ethosomes 显着提高了 A375 人类黑色素瘤细胞系的细胞毒性和细胞摄取。集落形成试验结果表明姜黄素乙醇小体具有优异的抗增殖作用，因为它们有效地抑制了 A375 细胞的克隆形成能力。流式细胞术结果表明姜黄素乙醇小体通过凋亡机制诱导A375细胞死亡。