Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Life Sci. 2022 Jun 1;298:120500. doi: 10.1016/j.lfs.2022.120500. Epub 2022 Mar 24.
Ferulic acid is a polyphenolic compound with proven anticancer properties, but it suffers from low solubility and bioavailability. In the current work, polymeric and lipidic nanocapsules of ferulic acid were prepared, characterized, and tested on colorectal cancer (CRC) cell lines (HCT-116 and Caco2 cells), with mechanistic anticancer elucidation using flow cytometry. The selected NCs formulation was further tested in vivo on rats after inducing CRC using 1,2 dimethylhydrazine (DMH), followed by biochemical analysis, molecular and histological examinations.
Results revealed that both polymeric and lipidic nanocapsules showed favorable properties, but the latter was smaller in size and presented higher cumulative percent released of FA. The lipidic nanocapsules displayed better anticancer activity than the drug on both cell lines; with apoptosis being the dominant cell death mode. The in vivo study revealed that ferulic acid lipid NCs exhibited significant antioxidant and anti-inflammatory activities. They also downregulated cyclin D1, IGF II, and VEGF, and autoregulated the apoptotic/anti-apoptotic gene BAX/Bcl-2; indicating their apoptotic and anti-angiogenic potential, which was further confirmed by histological examination.
Findings prove that the proposed ferulic acid lipid nanocapsules are an ideal system for treatment of CRC, and can serve as a preventive measure against metastasis.
阿魏酸是一种具有抗癌特性的多酚化合物，但它的溶解度和生物利用度较低。在目前的工作中，制备了阿魏酸的聚合物和脂质纳米胶囊，并对结直肠癌细胞系（HCT-116 和 Caco2 细胞）进行了测试，同时使用流式细胞术对其抗癌机制进行了阐明。在使用 1,2-二甲基肼（DMH）诱导大鼠结直肠癌后，选择的 NCs 制剂进一步在体内进行了测试，随后进行了生化分析、分子和组织学检查。
结果表明，聚合物和脂质纳米胶囊都表现出良好的性质，但后者的粒径更小，且 FA 的累积释放百分比更高。脂质纳米胶囊在两种细胞系上均显示出比药物更好的抗癌活性；凋亡是主要的细胞死亡模式。体内研究表明，阿魏酸脂质 NCs 表现出显著的抗氧化和抗炎活性。它们还下调了细胞周期蛋白 D1、IGF II 和 VEGF，并自动调节凋亡/抗凋亡基因 BAX/Bcl-2；表明它们具有凋亡和抗血管生成的潜力，这通过组织学检查得到了进一步证实。
研究结果证明，所提出的阿魏酸脂质纳米胶囊是治疗结直肠癌的理想体系，可作为预防转移的措施。
