基于“Lock-in”化学传递系统的脑靶向性前药研究进展

Advances in Brain-targeting Prodrugs based on “Lock-in” Chemical Delivery System

血脑屏障的存在,可使95%以上的药物不能有效地进入脑组织发挥作用.因此,基于提高血脑屏障透过能力,改善脑摄取特性的药物传递系统已经成为当前医药界最为关注的问题之一.自1958年Albert首次提出＂前药＂概念以来,前药修饰在提高口服药物生物利用度、改善组织分布、降低不良反应等方面均有着良好的应用,大约5%~7%的上市药物可以定义为前药.＂Lock-in＂化学传递系统是一种前药载体,能生成极性较大的中间体将药物＂Lock＂在脑内,从而可实现药物的脑靶向.本文综述了基于＂Lock-in＂化学传递系统的脑靶向性前药,包括二氢吡啶型、（酰氧基）烷基-磷酸酯型、硫胺素-二硫化物型等化学传递系统.

The majority of therapeutic drugs failed to get into the brain effectively owing to the existence of blood brainbarrier（ BBB）. Consequently,the development of drugs with improved brain uptake remains an ongoing concern. The concept of ＂Prodrug＂was proposed by Albert in 1958,since then,prodrugs have been usually designed to increase oral bioavailability,improve tissue-selective delivery,and reduce the side effects of a drug. 5-7% of commercially available drugs can be classified as prodrugs. Chemical delivery system（ CDS）,a kind of prodrug carrier,exhibited favourable brain-targeting properties since its polar intermediate,which can＂trap＂drugs in brain. In present paper,brain-targeting prodrugs based on CDS were reviewed,including dihydropyridine type,（ acyloxy） alkyl-phosphonate type,and thiamine-disulphide type,etc.