Dubashynskaya Natallia V, Bokatyi Anton N, Skorik Yury A
Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoy pr. V.O. 31, 199004 St. Petersburg, Russia.
Biomedicines. 2021 Mar 27;9(4):341. doi: 10.3390/biomedicines9040341.
Dexamethasone (DEX) is the most commonly prescribed glucocorticoid (GC) and has a wide spectrum of pharmacological activity. However, steroid drugs like DEX can have severe side effects on non-target organs. One strategy to reduce these side effects is to develop targeted systems with the controlled release by conjugation to polymeric carriers. This review describes the methods available for the synthesis of DEX conjugates (carbodiimide chemistry, solid-phase synthesis, reversible addition fragmentation-chain transfer [RAFT] polymerization, click reactions, and 2-iminothiolane chemistry) and perspectives for their medical application as GC drug or gene delivery systems for anti-tumor therapy. Additionally, the review focuses on the development of DEX conjugates with different physical-chemical properties as successful delivery systems in the target organs such as eye, joint, kidney, and others. Finally, polymer conjugates with improved transfection activity in which DEX is used as a vector for gene delivery in the cell nucleus have been described.
地塞米松（DEX）是最常用的糖皮质激素（GC），具有广泛的药理活性。然而，像DEX这样的类固醇药物会对非靶器官产生严重的副作用。减少这些副作用的一种策略是开发通过与聚合物载体偶联实现控释的靶向系统。本综述描述了可用于合成DEX缀合物的方法（碳二亚胺化学、固相合成、可逆加成-断裂链转移[RAFT]聚合、点击反应和2-亚氨基硫杂环戊烷化学）及其作为GC药物或用于抗肿瘤治疗的基因递送系统的医学应用前景。此外，该综述重点介绍了具有不同物理化学性质的DEX缀合物作为在眼睛、关节、肾脏等靶器官中成功递送系统的开发情况。最后，还描述了其中DEX用作细胞核基因递送载体、具有改善转染活性的聚合物缀合物。
