肝靶向核苷类逆转录酶抑制剂HepDirect前药的研究进展

靶向给药能够增加局部药物的浓度,提高疗效,减少不良反应。目前实现药物靶向性的重要策略是使用靶向载体,如抗体、肽、天然或人工合成的聚合物、糖或肽标记的毫微粒和脂质体等。但这些方法有很多不足,如难以通过内皮细胞到达血管外靶点、生产成本高、共轭物诱导免疫原反应、载药量有限及给药方式不便等。Erion等人发现了一类新的磷酸酯和膦酸酯前药,取名为HepDirect前药。该类前药可以特异性地被肝细胞CYP450同工酶CYP3A4酶氧化,释放活性形式的核苷酸或核苷膦酸。经动物和人体试验,HepDirect前药具有明显的肝靶向性,未发现与副产物相关的毒性。文中通过查阅近几年的相关文献,对核苷类HepDirect前药的原理、稳定性、副产物、代表药物等进行综述。

Advance in development of HepDirect prodrugs,liver targeting nucleoside reverse transcriptase inhibitors

The drugs targeting specific organs,tissues or cells can enhance drug efficacy and reduce adverse effects.Targeting can be achieved by carriers such as antibodies,peptides,natural and synthetic polymers,and carbohydrate-or peptide-labeled nanoparticles and liposomes.However,there are lots of disadvantages in above means.Drug exposure to extravascular sites often limits drug-conjugate exchange across the endothelial barrier.Advances of drug conjugates remain slow,which is due to higher manufacturing costs,co...