Abstract

Ethosomes are most commonly used vesicular delivery system compared to other lipidic vesicles due to its ethanolic content. Thymoquinone (TQ), the main biologically active complex of Black Cumin seed, has established anticancer activities in several tumors. In this work, the preparation of ethosome for TQ encapsulation by response surface method (RSM) was developed. Central composite design (CCD) was used to optimize three effective parameters involved in ethosome structure including phospholipid, cholesterol and ethanol concentration and the combined effects of them, as well. The obtained optimum values for the variables were phospholipid 5% (W/W), ethanol 45% (V/V) and cholesterol 1.5% (W/W) which were validated by experimental assay. The ethosomal formulation was more characterized for vesicle shape, size, zeta potential and entrapment efficiency percentage. The result showed an efficiency of 99% for drug entrapment with average vesicle size and zeta potential of 20 ± 1 nm and − 63 ± 2 mv, respectively. A quadratic model with a high adequacy (R²) for size and zeta potential of 0.9319 and 0.9338, respectively, was resulted from RSM and experimental assay. Thymoquinone (TQ) encapsulated in optimized ethosome. Also, cellular toxicity and release test was done. The toxicity and release curves were obtained and the cytotoxic activity of the ethosomic TQ against MCF-7 cell lines was greater than free TQ. IC50 values of free TQ, ethosomic TQ, were found to be 1.10 µg/ml, 0.95 µg/ml, respectively. The generated model suggests a new approach to prediction and experimental lipidic carriers.

Graphic abstract

Central composite design (CCD) was used to optimize three effective parameters involved in ethosome structure including phospholipid, cholesterol and ethanol concentration and the combined effects of them, as well. The ethosomal formulation was more characterized for vesicle shape, size, zeta potential and entrapment efficiency percentage. Also, cellular toxicity and release test was done. The toxicity and release curves were obtained and the cytotoxic activity of the ethosomic TQ against MCF-7 cell lines was greater than free TQ.

中文翻译：

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胸腺嘧啶核糖体具有乳腺癌的潜力：优化，体外和生物学评估

摘要

与其他脂质囊泡相比，由于乙醇含量高，因此，囊泡是最常用的囊泡递送系统。百里香酚（TQ）是黑孜然种子的主要生物活性复合物，已在多种肿瘤中建立了抗癌活性。在这项工作中，开发了通过响应面法（RSM）制备TQ封装用的核糖体。中央复合设计（CCD）用于优化涉及核糖体结构的三个有效参数，包括磷脂，胆固醇和乙醇的浓度以及它们的综合作用。获得的变量最佳值是磷脂5％（W / W），乙醇45％（V / V）和胆固醇1.5％（W / W），这些均已通过实验验证。气管制剂的囊泡形状，大小，Zeta电位和截留效率百分比。结果显示，平均囊泡大小和ζ电位分别为20±1 nm和-63±2 mv的药物截留效率为99％。具有足够高的二次模型（通过RSM和实验分析得出的大小和Zeta电位的R ²）分别为0.9319和0.9338。胸腺醌（TQ）封装在优化的脂质体中。另外，进行了细胞毒性和释放测试。获得了毒性和释放曲线，并且内质性TQ对MCF-7细胞系的细胞毒性活性大于游离TQ。游离TQ，内生TQ的IC50值分别为1.10 µg / ml，0.95 µg / ml。生成的模型提出了预测和实验脂质载体的新方法。

图形摘要

中央复合设计（CCD）用于优化涉及脂质体结构的三个有效参数，包括磷脂，胆固醇和乙醇的浓度以及它们的综合作用。气管制剂的囊泡形状，大小，ζ电势和包封效率百分比更具特征。另外，进行了细胞毒性和释放测试。获得了毒性和释放曲线，并且内质性TQ对MCF-7细胞系的细胞毒性活性大于游离TQ。