Wong Kar En, Ngai Siew Ching, Chan Kok-Gan, Lee Learn-Han, Goh Bey-Hing, Chuah Lay-Hong
Biofunctional Molecule Exploratory Research Group, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia.
Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia.
Front Pharmacol. 2019 Mar 5;10:152. doi: 10.3389/fphar.2019.00152. eCollection 2019.
Colorectal cancer (CRC) is the third most prevalent form of cancer, after lung cancer and breast cancer, with the second highest death incidence. Over the years, natural compounds have been explored as an alternative to conventional cancer therapies such as surgery, radiotherapy, and chemotherapy. Curcumin, an active constituent of turmeric has been associated with various health benefits. It has gained much attention as an anticancer agent due to its ability to regulate multiple cell signaling pathways, including NF-κB, STAT3, activated protein-1 (AP-1), epidermal growth response-1 (Egr-1), and p53, which are crucial in cancer development and progression. Nevertheless, the clinical application of curcumin is greatly restricted because of its low water solubility, poor oral absorption, and rapid metabolism. These issues have led to the development of curcumin nanoformulations to overcome the limitations of the compound. Nanotechnology-based delivery systems have been widely used in improving the delivery of poorly-water soluble drugs. Besides, these systems also come with the added benefits of possible cellular targeting and improvement in cellular uptake. An ideal improved formulation should display a greater anticancer activity compared to free curcumin, and at the same time be non-toxic to the normal cells. In this review, we focus on the design and development of various nanoformulations to deliver curcumin for use in CRC such as liposomes, micelles, polymer nanoparticles, nanogels, cyclodextrin complexes, solid lipid nanoparticles (SLN), phytosomes, and gold nanoparticles. We also discuss the current pre-clinical and clinical evidences of curcumin nanoformulations in CRC therapy, analyse the research gap, and address the future direction of this research area.
结直肠癌(CRC)是继肺癌和乳腺癌之后第三大常见癌症,其死亡发病率位居第二。多年来,天然化合物已被探索作为手术、放疗和化疗等传统癌症疗法的替代方案。姜黄素是姜黄的一种活性成分,具有多种健康益处。由于其能够调节多种细胞信号通路,包括在癌症发生和发展中起关键作用的核因子-κB(NF-κB)、信号转导和转录激活因子3(STAT3)、活化蛋白-1(AP-1)、表皮生长反应-1(Egr-1)和p53,它作为一种抗癌剂受到了广泛关注。然而,由于姜黄素水溶性低、口服吸收差以及代谢迅速,其临床应用受到极大限制。这些问题促使了姜黄素纳米制剂的开发,以克服该化合物的局限性。基于纳米技术的递送系统已被广泛用于改善水溶性差的药物的递送。此外,这些系统还具有可能的细胞靶向和细胞摄取改善等额外益处。一种理想的改进制剂应比游离姜黄素表现出更强的抗癌活性,同时对正常细胞无毒。在本综述中,我们重点关注用于结直肠癌的各种递送姜黄素的纳米制剂的设计和开发,如脂质体、胶束、聚合物纳米颗粒、纳米凝胶、环糊精复合物、固体脂质纳米颗粒(SLN)、植物脂质体和金纳米颗粒。我们还讨论了姜黄素纳米制剂在结直肠癌治疗中的当前临床前和临床证据,分析了研究差距,并探讨了该研究领域的未来方向。