The present study was designed to improve the aqueous solubility and dissolution rate of citreorosein, a poorly water soluble drug, by producing its nanoparticles (NPs) using an “antisolvent precipitation with a syringe pump” (APSP) method. Various process parameters including flow rate, stirring speed, temperature, drug concentration and solvent-antisolvent ratio were investigated and optimized to obtain the smallest particle size of citreorosein. The prepared NPs were subjected to different analytical techniques such as SEM, FTIR, XRD and DLS. The NPs were tested for different dissolution parameters including difference (f) and similarity factors (f), dissolution efficiency (DE) and mean dissolution time (MDT). The antioxidant potential of citreorosein and its NPs were evaluated using DPPH, ABTS, and FRAP models, while their cytotoxicity was tested on various cancer cell lines such as breast (MDA-MB-231), lung (A549) and liver (HepG2), using the MTT assay. The specificity of the test compound was investigated against two normal human primary epithelial cells including renal (HRPTEpiC) and alveolar (HPAEpiC) cells. DLS analysis revealed that the prepared NPs were less than 200 nm in size while SEM and XRD confirmed their rod shape and amorphous nature, respectively. Citreorosein-NPs exhibited enhanced solubility and dissolution rate in all medias as compared to pure citreorosein. The NPs displayed significant antioxidant effects against ABTS, DPPH and FRAP models, with IC values of22.6, 21.45 and 27.30 µg/ml, respectively. Moreover, it showed significant cytotoxic activity against MDA-MB-231, A549 and HepG2 cells, with IC values of 3.45, 4.5 and 6.23 µg/ml, respectively. Furthermore, the NPs demonstrated high selectivity index values for the aforementioned cell lines as compared to reference drugs. This study demonstrated that APSP method successfully produced citreorosein-NPs and hence, showed better aqueous solubility, dissolution rate, antioxidant and cytotoxic activities than the pure compound.

中文翻译：

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具有改善的生物利用度和细胞毒性潜力的柠檬黄纳米颗粒的制备和表征

本研究旨在通过使用“注射泵反溶剂沉淀”（APSP）方法生产其纳米颗粒（NP），提高柠檬黄（一种难溶于水的药物）的水溶性和溶出率。研究并优化了各种工艺参数，包括流速、搅拌速度、温度、药物浓度和溶剂-反溶剂比，以获得最小粒径的柠檬黄。对制备的纳米颗粒进行不同的分析技术，如SEM、FTIR、XRD 和DLS。测试了纳米颗粒的不同溶出参数，包括差异因子 (f) 和相似因子 (f)、溶出效率 (DE) 和平均溶出时间 (MDT)。使用 DPPH、ABTS 和 FRAP 模型评估了柠檬黄素及其 NP 的抗氧化潜力，同时在多种癌细胞系（如乳腺癌 (MDA-MB-231)、肺癌 (A549) 和肝癌 (HepG2)）上测试了它们的细胞毒性。使用 MTT 测定。研究了测试化合物针对两种正常人原代上皮细胞的特异性，包括肾细胞 (HRPTEpiC) 和肺泡细胞 (HPAEpiC)。 DLS 分析显示所制备的纳米颗粒尺寸小于 200 nm，而 SEM 和 XRD 分别证实了它们的棒状和无定形性质。与纯柠檬黄相比，柠檬黄-纳米粒子在所有介质中都表现出增强的溶解度和溶出速率。 NPs 对 ABTS、DPPH 和 FRAP 模型表现出显着的抗氧化作用，IC 值分别为 22.6、21.45 和 27.30 µg/ml。此外，它对 MDA-MB-231、A549 和 HepG2 细胞表现出显着的细胞毒活性，IC 值分别为 3.45、4.5 和 6.23 µg/ml。此外，与参考药物相比，纳米颗粒对上述细胞系表现出高选择性指数值。这项研究表明，APSP 方法成功生产了柠檬黄-纳米颗粒，因此比纯化合物表现出更好的水溶性、溶出率、抗氧化和细胞毒活性。