Background: Colorectal cancer (CRC) is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women. Curcumin (CMN) is obtained from a natural source and has no toxicity, even at high doses (8,000 mg/kg body weight in 24 hours) and was determined to have anticancer potency on several kinds of carcinoma. However, its medical applications were limited because of its low solubility and poor bioavailability.
Materials and Methods: To improve the medical applications of CMN, various hydrophilic carriers such as poloxamer 407 (PMX-407), poloxamer 188 (PMX-188), Gelucire 50/13 (Gel-50/13), and mannitol (MNL) were used to prepare a binary complex solid dispersion (SD). These binary SDs were characterized for aqueous solubility in various solvents. Physical stability, thermal behaviors, and morphology were determined by Fourier transform infrared spectrophotometric analysis, powder X-ray diffraction analysis, thermogravimetric analysis, differential scanning calorimetric analysis, scanning electron microscopy, dynamic light scattering study, and the novel dyeing test. In vitro drug release was determined by dissolution study. Based on the characterization, the better SD complex was optimized using Box-Behnken design (BBD). The cytotoxicity and apoptosis study of prepared CMN (C-SD) were used to test for colorectal adenocarcinoma cell lines.
Results: These results showed that the solubility of CMN is greatly improved after complexation with PXM-407 in SD. CMN is practically insoluble in water at acidic and neutral pH; however, the SD of CMN with PXM-407 produced significant improvement in solubility (1.266± 0.0242 mg/mL) and dissolution (91.36± 0.431% at 30 minutes); similarly, these data fit with a phase solubility study and in silico molecular modeling. Moreover, the solid-state characterization revealed that the SD complex exhibits the intermolecular hydrogen bond with drug and carrier. Also, the complex does not undergo any chemical modification owing to the amorphous form, and the dye test showed better coloring impact indicating the solubility of CMN. The cell cycle arrest confirmed at G2/M phase from flow cytometry analysis, and Western blot investigation was recognized molecular level cell death and the complex induced more exploit DNA during apoptosis.
Conclusion: This study confirmed that the ideal stoichiometric ratio of CMN with carrier to enhance its solubility was 1:1. This molecular complex of PXM-407 was found to be more effective against colorectal cancer (CRC) than pure CMN.



中文翻译：

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化学计量控制的姜黄素固体分散体及其对结直肠腺癌细胞的细胞毒性评价

背景：结直肠癌 (CRC) 是男性中第三大最常见的癌症，也是女性中第二常见的癌症。姜黄素 (CMN) 是从天然来源获得的，即使在高剂量（24 小时内 8,000 mg/kg 体重）下也没有毒性，并且被确定对多种癌症具有抗癌效力。然而，由于其溶解度低和生物利用度差，其医学应用受到限制。
材料和方法：为提高CMN的医学应用，采用泊洛沙姆407（PMX-407）、泊洛沙姆188（PMX-188）、Gelucire 50/13（Gel-50/13）和甘露醇（MNL）等亲水性载体制备二元复合固体分散体 (SD)。这些二元 SD 的特征在于在各种溶剂中的水溶性。通过傅里叶变换红外分光光度分析、粉末X射线衍射分析、热重分析、差示扫描量热分析、扫描电子显微镜、动态光散射研究和新型染色试验确定物理稳定性、热行为和形态。通过溶出研究确定体外药物释放。基于表征，使用 Box-Behnken 设计 (BBD) 优化了更好的 SD 复合体。
结果：这些结果表明，在 SD 中与 PXM-407 络合后，CMN 的溶解度大大提高。CMN 在酸性和中性 pH 值下几乎不溶于水；然而，CMN 与 PXM-407 的 SD 对溶解度 (1.266± 0.0242 mg/mL) 和溶出度 (30 分钟时为 91.36± 0.431%) 产生了显着改善；同样，这些数据符合相溶解度研究和计算机分子建模。此外，固态表征表明SD复合物与药物和载体表现出分子间氢键。此外，由于无定形形式，该复合物未发生任何化学修饰，染料测试显示更好的着色影响，表明 CMN 的溶解度。流式细胞仪分析证实细胞周期停滞在 G2/M 期，
结论：本研究证实，CMN 与载体提高其溶解度的理想化学计量比为 1:1。发现这种 PXM-407 分子复合物对结直肠癌 (CRC) 比纯 CMN 更有效。