Design, Synthesis and Evaluation of Dual-targeting Prodrug Co-modified by Organic Amine and L-ascorbic Acid for CNS Delivery

Title:Design, Synthesis and Evaluation of Dual-targeting Prodrug Co-modified by Organic Amine and L-ascorbic Acid for CNS Delivery

Volume: 14 Issue: 9

Author(s): Shubing Qiu, Yi Zhao, Sha Liu, Xiaocen Li, Li Guo, Li Hai*Yong Wu*

Affiliation:

• Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041,China

• Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041,China

Keywords: Dual-brain targeting, drug delivery, organic amine, L-ascorbic acid, prodrug, CNS.

Abstract: 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.

Cite this article as:

Qiu Shubing, Zhao Yi, Liu Sha, Li Xiaocen, Guo Li, Hai Li*, Wu Yong*, Design, Synthesis and Evaluation of Dual-targeting Prodrug Co-modified by Organic Amine and L-ascorbic Acid for CNS Delivery, Letters in Drug Design & Discovery 2017; 14 (9) . https://dx.doi.org/10.2174/1570180814666161230161152

DOI https://dx.doi.org/10.2174/1570180814666161230161152	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X