Khan Haroon, Ullah Hammad, Martorell Miquel, Valdes Susana Esteban, Belwal Tarun, Tejada Silvia, Sureda Antoni, Kamal Mohammad Amjad
Department of Pharmacy, Abdul Wali Khan University, Mardan, 23200, Pakistan; Novel Global Community Educational Foundation, Australia.
Department of Pharmacy, Abdul Wali Khan University, Mardan, 23200, Pakistan; Novel Global Community Educational Foundation, Australia.
Semin Cancer Biol. 2021 Feb;69:200-211. doi: 10.1016/j.semcancer.2019.07.023. Epub 2019 Jul 30.
The conventional therapies for cancer have a major concern of poor accessibility to tumor tissues. Furthermore, the requirement of higher doses and non-selective nature of therapeutic are associated with a range of adverse drug reactions (ADRs). However, flavonoids are documented to be effective against various types of cancer, but they are not evaluated for their safety profile and tumor site-specific action. Low solubility, rapid metabolism and poor absorption of dietary flavonoids in gastrointestinal tract hinder their pharmacological potential. Some studies have also suggested that flavonoids may act as pro-oxidant in some cases and may interact with other therapeutic agents, especially through biotransformation. Nanocarriers can alter pharmacokinetics and pharmacodynamic profile of incorporating drug. Moreover, nanocarriers are designed for targeted drug delivery, improving the bioavailability of poorly water-soluble drugs, delivery of macromolecules to site of action within the cell, combining therapeutic agents with imaging techniques which may visualize the site of drug delivery and co-delivery of two or more drugs. Combining two or more anti-cancer agents can reduce ADRs and nanotechnology played a pivotal role in this regard. In vitro and in vivo studies have shown the potential of flavonoids nano-formulations, especially quercetin, naringenin, apigenin, catechins and fisetin in the prevention and treatment of several types of cancer. Similarly, clinical trials have been conducted using flavonoids alone or in combination, however, the nano-formulations effect still needs to be elucidated. This review focuses on the impact of flavonoids nano-formulations on the improvement of their bioavailability, therapeutic and safety profile and will open new insights in the field of drug discovery for cancer therapeutics.
癌症的传统疗法主要存在肿瘤组织难以到达的问题。此外,治疗所需的高剂量以及治疗的非选择性与一系列药物不良反应(ADR)相关。然而,黄酮类化合物已被证明对多种类型的癌症有效,但尚未对其安全性和肿瘤部位特异性作用进行评估。膳食黄酮类化合物在胃肠道中的低溶解度、快速代谢和吸收不良阻碍了它们的药理潜力。一些研究还表明,黄酮类化合物在某些情况下可能作为促氧化剂,并且可能与其他治疗剂相互作用,尤其是通过生物转化。纳米载体可以改变所载入药物的药代动力学和药效学特征。此外,纳米载体被设计用于靶向给药,提高难溶性药物的生物利用度,将大分子递送至细胞内的作用部位,将治疗剂与成像技术相结合,从而可以可视化药物递送部位以及两种或更多种药物的共递送。联合使用两种或更多种抗癌药物可以减少药物不良反应,而纳米技术在这方面发挥了关键作用。体外和体内研究表明,黄酮类化合物纳米制剂,尤其是槲皮素、柚皮素、芹菜素、儿茶素和漆黄素在预防和治疗多种类型癌症方面具有潜力。同样,已经进行了单独使用或联合使用黄酮类化合物的临床试验,然而,纳米制剂的效果仍有待阐明。本综述重点关注黄酮类化合物纳米制剂对提高其生物利用度、治疗效果和安全性的影响,并将为癌症治疗药物发现领域开辟新的见解。