Faculty of Medicine, Amsterdam UMC, Location Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam University Medical Center, Location Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Eur J Drug Metab Pharmacokinet. 2021 Nov;46(6):743-758. doi: 10.1007/s13318-021-00716-x. Epub 2021 Sep 6.
Thiopurines (mercaptopurine, azathioprine and thioguanine) are well-established maintenance treatments for a wide range of diseases such as leukemia, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and other inflammatory and autoimmune diseases in general. Worldwide, millions of patients are treated with thiopurines. The use of thiopurines has been limited because of off-target effects such as myelotoxicity and hepatotoxicity. Therefore, seeking methods to enhance target-based thiopurine-based treatment is relevant, combined with pharmacogenetic testing. Controlled-release formulations for thiopurines have been clinically tested and have shown promising outcomes in inflammatory bowel disease. Latest developments in nano-formulations for thiopurines have shown encouraging pre-clinical results, but further research and development are needed. This review provides an overview of novel drug delivery strategies for thiopurines, reviewing modified release formulations and with a focus on nano-based formulations.
硫嘌呤（巯嘌呤、硫唑嘌呤和硫鸟嘌呤）是广泛应用于治疗白血病、炎症性肠病（IBD）、系统性红斑狼疮（SLE）和其他一般炎症性及自身免疫性疾病的成熟维持治疗药物。在全球范围内，数以百万计的患者正在接受硫嘌呤治疗。由于存在骨髓毒性和肝毒性等非靶向作用，硫嘌呤的应用受到限制。因此，寻找增强基于硫嘌呤的靶向治疗的方法是相关的，结合药物遗传学检测。硫嘌呤的控释制剂已经在临床上进行了测试，并在炎症性肠病中显示出有希望的结果。硫嘌呤的纳米制剂的最新发展显示出令人鼓舞的临床前结果，但仍需要进一步的研究和开发。本文综述了硫嘌呤的新型药物传递策略，综述了改良释放制剂，并重点介绍了基于纳米的制剂。
