Dual-targeting for brain-specific drug delivery: synthesis and biological evaluation.
Dual-targeting for brain-specific drug delivery: synthesis and biological evaluation.
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脑特异性药物递送的双靶向：合成和生物学评价
DOI：
10.1080/10717544.2018.1431978
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发表时间：
2018-11
期刊：
影响因子：
6
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Yue Q;Peng Y;Zhao Y;Lu R;Fu Q;Chen Y;Yang Y;Hai L;Guo L;Wu Y
摘要布洛芬是最有效的非甾体抗炎药之一，在神经退行性疾病的治疗中发挥着重要作用。然而，其较差的脑渗透性和治疗剂量下的严重副作用阻碍了其进一步应用。因此，开发一种载体介导的转运蛋白（CMT）系统是非常有意义的，该系统能够以较小的剂量更有效地将布洛芬递送到大脑中以治疗神经退行性疾病。本研究设计并合成了一种葡萄糖（Glu）和维生素C（Vc）修饰的布洛芬中枢神经系统（CNS）药物双介导前药，以实现布洛芬的脑内给药。当与各种缓冲液、小鼠血浆和脑匀浆孵育时，可从所制备的前药中释放出I β。此外，前体药物在体外和体内显示出比布洛芬更上级的神经保护作用。我们的结果表明，用葡萄糖和VC弹头对治疗剂进行化学修饰是利用弹头的内源性运输机制开发脑靶向前药的一种有前途且有效的策略。
Abstract Ibuprofen is one of the most potent non-steroid anti-inflammatory drugs (NSAIDs) and plays an important role in the treatment of neurodegenerative diseases. However, its poor brain penetration and serious side effects at therapeutic doses, has hindered its further application. Thus, it is of great interest to develop a carrier-mediated transporter (CMT) system that is capable of more efficiently delivering ibuprofen into the brain at smaller doses to treat neurodegenerative diseases. In this study, a dual-mediated ibuprofen prodrug modified by glucose (Glu) and vitamin C (Vc) for central nervous system (CNS) drug delivery was designed and synthesized in order to effectively deliver ibuprofen to brain. Ibuprofen could be released from the prepared prodrugs when incubated with various buffers, mice plasma and brain homogenate. Also, the prodrug showed superior neuroprotective effect in vitro and in vivo than ibuprofen. Our results suggest that chemical modification of therapeutics with warheads of glucose and Vc represents a promising and efficient strategy for the development of brain-targeting prodrugs by utilizing the endogenous transportation mechanism of the warheads.
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具有高亲和力的多价糖苷作为脑靶向脂质体配体的设计、合成和生物学评价。
影响因子：
6.7
作者：
Qu, Boyi;Li, Xiaocen;Wu, Yong
通讯作者：
Wu, Yong
DOI：
10.3390/molecules13051035
发表时间：
2008-05-01
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Pavan B;Dalpiaz A;Ciliberti N;Biondi C;Manfredini S;Vertuani S
通讯作者：
Vertuani S
影响因子：
4.7
作者：
Teema, Asmaa M.;Zaitone, Sawsan A.;Moustafa, Yasser M.
通讯作者：
Moustafa, Yasser M.
阿霉素和长春新碱的双重修饰脂质体共递送可提高神经胶质瘤的靶向和治疗效果。
影响因子：
6
作者：
Zhang Y;Zhai M;Chen Z;Han X;Yu F;Li Z;Xie X;Han C;Yu L;Yang Y;Mei X
通讯作者：
Mei X
影响因子：
9.1
作者：
Wu, Xue-Ying;Li, Xiao-Cen;Hai, Li
通讯作者：
Hai, Li