Key Laboratory of Drug Targeting and Drug Delivery System of Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, P. R. China.
Arch Pharm (Weinheim). 2018 May;351(5):e1700382. doi: 10.1002/ardp.201700382. Epub 2018 Mar 22.
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.
为了将萘普生有效递送至脑部，设计并合成了一种新的、将葡萄糖和抗坏血酸与萘普生连接而成的双重靶向萘普生前药。该前药在与各种缓冲液、鼠血浆和脑匀浆孵育时，萘普生可从所制备的前药中释放出来。此外，该前药在体内的神经保护作用优于萘普生。我们的结果表明，通过利用弹头的内源性转运机制，用葡萄糖和抗坏血酸的弹头对治疗药物进行化学修饰，代表了开发脑靶向前药的一种有前途且有效的策略。
