Design, synthesis, and neuroprotective effects of dual‐brain targeting naproxen prodrug
Design, synthesis, and neuroprotective effects of dual‐brain targeting naproxen prodrug
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DOI：
10.1002/ardp.201700382
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发表时间：
2018-05
影响因子：
5.1
通讯作者：
Linhui Wang;Li Zhang;Yi Zhao;Qiuyi Fu;Wenjiao Xiao;Runxin Lu;Li Hai;Li Guo;Yong Wu
中科院分区：
文献类型：
--
作者：
Linhui Wang;Li Zhang;Yi Zhao;Qiuyi Fu;Wenjiao Xiao;Runxin Lu;Li Hai;Li Guo;Yong Wu
设计并合成了一种用于中枢神经系统（CNS）药物递送的与葡萄糖和抗坏血酸缀合的新型双靶向萘普生前药，以有效地将萘普生递送至大脑。当与各种缓冲液、小鼠血浆和脑匀浆孵育时，可以从制备的前药中释放出萘普生。此外，该前药在体内显示出优于萘普生的上级神经保护作用。我们的研究结果表明，化学修饰的治疗与弹头的葡萄糖和抗坏血酸是一个有前途的和有效的策略，通过利用内源性运输机制的弹头的脑靶向前药的发展。
A new dual‐targeting naproxen prodrug conjugated with glucose and ascorbic acid for central nervous system (CNS) drug delivery was designed and synthesized in order to effectively deliver naproxen to the brain. Naproxen could be released from the prepared prodrugs when incubated with various buffers, mouse plasma, and brain homogenate. Also, the prodrug showed superior neuroprotective effect in vivo over naproxen. Our results suggest that chemical modification of therapeutics with warheads of glucose and ascorbic acid represents a promising and efficient strategy for the development of brain targeting prodrugs by utilizing the endogenous transportation mechanism of the warheads.