Design, Synthesis and Evaluation of Dual-targeting Prodrug Co-modified by Organic Amine and L-ascorbic Acid for CNS Delivery
Design, Synthesis and Evaluation of Dual-targeting Prodrug Co-modified by Organic Amine and L-ascorbic Acid for CNS Delivery
复制标题
有机胺和L-抗坏血酸共修饰用于中枢神经系统递送的双靶向前药的设计、合成和评价
DOI：
10.2174/1570180814666161230161152
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发表时间：
2017-01-01
影响因子：
1
通讯作者：
Wu, Yong
中科院分区：
文献类型：
--
作者：
Qiu, Shubing;Zhao, Yi;Wu, Yong
背景：l -抗坏血酸和有机胺具有良好的脑靶向能力。然而，l -抗坏血酸与有机胺联合作为中枢神经系统给药载体的研究尚未见报道。目的：合成有机胺与l -抗坏血酸共修饰的布洛芬前药，并评价其脑靶向性。方法：设计合成了有机胺与l-抗坏血酸共修饰的双靶向布洛芬前药2。用HEK293T细胞评价细胞毒性。分别在缓冲液、血浆和脑匀浆中研究其化学和代谢稳定性。并与前药1和裸布洛芬在体内进行脑靶向性比较。结果：新型前药2具有良好的穿透脑血屏障（BBB）的能力，能显著提高脑内布洛芬水平。其相对吸收效率和浓缩效率分别是裸布洛芬的3.16倍和4.92倍。结论：有机胺和l -抗坏血酸是促进中枢神经系统药物向脑传递的良好载体。这些结果为开发新的脑靶向药物提供了一个有效的切入点。
Background: L-ascorbic acid and organic amine showed a good brain targeting ability. However, there was no report on the combination of L-ascorbic acid and organic amine as a carrier for central nervous system (CNS) drug delivery.Objective: To synthesize the ibuprofen prodrug co-modified by organic amine and L-ascorbic acid, and evaluate its brain targeting ability.Methods: A dual-targeting ibuprofen prodrug 2 co-modified by organic amine and L-ascorbic acid was designed and synthesized. HEK293T cells were used to evaluate the cytotoxicity. The chemical and metabolic stability was investigated in buffer solutions, plasma and brain homogenate, respectively. Furthermore, the brain targeting ability of the prodrug was evaluated in vivo compared with prodrug 1 and naked ibuprofen.Results: The novel prodrug 2 exhibited excellent ability to penetrate the brain-blood barrier (BBB) and significantly increased the level of ibuprofen in brain. The relative uptake efficiency and concentration efficiency were enhanced by 3.16 and 4.92 times than that of naked ibuprofen, respectively.Conclusion: The results of this study indicated that organic amine and L-ascorbic acid was a splendid carrier to enhance the delivery of CNS drugs into brain. These results provided an effective entry to the development of new brain targeting drugs.