Wiggins Russell, Woo Jihoo, Mito Shizue
Department of Medical Education, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78541, USA.
Cancers (Basel). 2024 Oct 21;16(20):3548. doi: 10.3390/cancers16203548.
Inhibition of multiple cancer-related pathways has made niclosamide a promising candidate for the treatment of various cancers. However, its clinical application has been significantly limited by poor bioavailability. This review will discuss current findings on improving niclosamide bioavailability through modification of its chemical structure and utilization of novel nanotechnologies, like electrospraying and supercritical fluids, to improve drug delivery. For example, niclosamide derivatives, such as o-alkylamino-tethered niclosamide derivates, niclosamide ethanolamine salt, and niclosamide piperazine salt, have demonstrated increased water solubility without compromising anticancer activity in vitro. Additionally, this review briefly discusses recent findings on the first pass metabolism of niclosamide in vivo, the role of cytochrome P450-mediated hydroxylation, UDP-glucuronosyltransferase mediated glucuronidation, and how enzymatic inhibition could enhance niclosamide bioavailability. Ultimately, there is a need for researchers to synthesize, evaluate, and improve upon niclosamide derivatives while experimenting with the employment of nanotechnologies, such as targeted delivery and nanoparticle modification, as a way to improve drug administration. Researchers should strive to improve drug-target accuracy, its therapeutic index, and increase the drug's efficacy as an anti-neoplastic agent.
对多种癌症相关途径的抑制作用使氯硝柳胺成为治疗多种癌症的一个有前景的候选药物。然而，其临床应用因生物利用度差而受到显著限制。本综述将讨论通过修饰氯硝柳胺的化学结构以及利用新型纳米技术（如电喷雾和超临界流体）来改善药物递送从而提高氯硝柳胺生物利用度的当前研究结果。例如，氯硝柳胺衍生物，如邻烷基氨基连接的氯硝柳胺衍生物、氯硝柳胺乙醇胺盐和氯硝柳胺哌嗪盐，已证明在不损害体外抗癌活性的情况下增加了水溶性。此外，本综述简要讨论了氯硝柳胺在体内首过代谢的最新研究结果、细胞色素P450介导的羟基化作用、UDP-葡萄糖醛酸基转移酶介导的葡萄糖醛酸化作用，以及酶抑制如何提高氯硝柳胺的生物利用度。最终，研究人员需要合成、评估和改进氯硝柳胺衍生物，同时试验采用纳米技术（如靶向递送和纳米颗粒修饰）来改善药物给药。研究人员应努力提高药物靶向准确性、其治疗指数，并提高该药物作为抗肿瘤药物的疗效。
