Yang Jincheng, Jia Lirui, He Zhonggui, Wang Yongjun
Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, PR China; R&D Department, Ningxia Kangya Pharmaceutical Co., Ltd, Yinchuan 750002, PR China.
Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Int J Pharm. 2023 Apr 25;637:122886. doi: 10.1016/j.ijpharm.2023.122886. Epub 2023 Mar 24.
DNA topoisomerase I plays a key role in lubricatingthe wheels of DNA replication or RNA transcription through breaking and reconnecting DNA single-strand. It is widely known that camptothecin and its derivatives (CPTs) have inhibitory effects on topoisomerases I, and have obtained some clinical benefits in cancer treatment. The potent cytotoxicity makes 7-ethyl-10-hydroxycamptothecin (SN-38) become a brilliant star among these derivatives. However, some undesirable physical and chemical properties of this compound, including poor solubility and stability, seriously hinder its effective delivery to tumor sites. In recent years, strategies to alleviate these defects have aroused extensive research interest. By focusing on the loading mechanism, basic nanodrug delivery systems with SN-38 loaded, like nanoparticles, liposomes and micelles, are demonstrated here. Additionally, functionalized nanodrug delivery systems of SN-38 including prodrug and active targeted nanodrug delivery systems and delivery systems designed to overcome drug resistance are also reviewed. At last, challenges for future research in formulation development and clinical translation of SN-38 drug delivery system are discussed.
DNA拓扑异构酶I通过断裂和重新连接DNA单链,在润滑DNA复制或RNA转录过程中发挥关键作用。众所周知,喜树碱及其衍生物(CPTs)对拓扑异构酶I具有抑制作用,并在癌症治疗中取得了一定的临床疗效。强大的细胞毒性使7-乙基-10-羟基喜树碱(SN-38)成为这些衍生物中的一颗璀璨明星。然而,该化合物一些不理想的物理和化学性质,包括溶解性和稳定性差,严重阻碍了其有效递送至肿瘤部位。近年来,缓解这些缺陷的策略引起了广泛的研究兴趣。本文通过聚焦负载机制,展示了负载SN-38的基本纳米药物递送系统,如纳米颗粒、脂质体和胶束。此外,还综述了SN-38的功能化纳米药物递送系统,包括前药、主动靶向纳米药物递送系统以及旨在克服耐药性的递送系统。最后,讨论了SN-38药物递送系统在制剂开发和临床转化方面未来研究面临的挑战。