纳米级脑靶向递药系统的靶向性提升策略  

Strategies for enhancing nanoscale brain targeting drug delivery

作　　者：黄梦瑶 杨旭[1] 邢金峰[1] 魏振平[1] HUANG Meng-yao;YANG Xu;XING Jin-feng;WEI Zhen-ping(School of Chemical Engineering, Tianjin University, Tianjin 300350, China)

机构地区：[1]天津大学化工学院,天津300350

出　　处：《药学学报》2019年第4期629-637,共9页Acta Pharmaceutica Sinica

基　　金：天津市自然科学基金资助项目(14JCYBJC29100)

摘　　要：血脑屏障能选择性阻滞外周血液中的物质进入脑内,这对于维持脑内环境稳定十分重要,但同时会阻碍治疗药物向脑内递送。被动脑靶向递药系统可以通过增强与血脑屏障细胞的亲和力及减弱P-糖基蛋白对药物的外排来提高脑内药物浓度;在被动靶向递药系统上结合特异性配体或抗体得到的主动脑靶向递药系统,能更精准地实现药物向脑内靶向递送;脑靶向联合肿瘤细胞靶向得到的双级靶向递药系统,对脑部肿瘤的治疗已显示出其独特优势。脑靶向递药系统将为阿尔茨海默病、脑肿瘤及中风等脑部疾病的治疗提供一种独特方式。在介绍被动型、主动型脑靶向及双级脑靶向递药系统的同时,本文重点对降低载体粒径、打开血脑屏障细胞间的紧密连接、于载体表面键合亲水性基团及鼻腔给药等提高药物脑内递送效率的策略进行了展望。The blood brain barrier can selectively block the uptake of xenobiotics from peripheral blood into the brain. Although this is important for maintaining the stability of the brain environment and normal function of the central nervous system, it presents a challenge for delivery of therapeutic drugs to the brain. Passive brain-targeting drug carrier is able to increase the drug concentration in the brain by enhancing the affinity to blood-brain barrier and/or inhibiting the efflux absorbed drug via P-glycoprotein. The active brain-targeting drug carrier can be obtained by linking specific ligands or antibodies onto passive target carriers to achieve precise delivery of drugs to the brain. Dual targeting drug carriers obtained by combining tumor cell targeting with brain targeting have shown their advantages for treatment of brain tumors. The targeted drug delivery to brain will provide a unique manner for the treatment of brain diseases such as Alzheimer's, Parkinson's, brain tumors, and stroke. Among the drug delivery systems of passive brain-targeting, active brain-targeting and dual brain-targeting, we evaluated the strategies to improve brain drug delivery efficiency, such as by reducing carrier size, opening tight junctions between cells at the blood-brain barrier, incorporating hydrophilic groups on the surface of the carrier, and alternative intranasal drug administration.

关 键 词：血脑屏障 纳米级 递药系统 双级脑靶向 靶向性提升策略 

分 类 号：R943[医药卫生—药剂学]