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.
氯硝柳胺通过抑制多种癌症相关通路，已成为治疗多种癌症的潜力候选药物。然而，其较差的生物利用度严重限制了临床应用。本综述将探讨当前通过化学结构修饰及新型纳米技术（如电喷雾和超临界流体技术）改善药物递送以提高氯硝柳胺生物利用度的研究进展。例如，氯硝柳胺衍生物（如邻位烷氨基修饰衍生物、氯硝柳胺乙醇胺盐及氯硝柳胺哌嗪盐）在保持体外抗癌活性的同时显著提升了水溶性。此外，本文简要综述了氯硝柳胺体内首过代谢的最新发现，包括细胞色素P450介导的羟化作用、UDP-葡萄糖醛酸转移酶介导的葡萄糖醛酸化作用，以及酶抑制策略如何提升其生物利用度。未来研究需在合成与评估氯硝柳胺衍生物的基础上，结合靶向递送和纳米颗粒修饰等纳米技术优化给药方案，致力于提升药物靶向精准度、治疗指数及抗肿瘤疗效。
肿瘤(癌症)患者之家