Format

Send to

Choose Destination
Eur J Med Chem. 2014 Jul 23;82:314-23. doi: 10.1016/j.ejmech.2014.05.072. Epub 2014 Jun 2.

Design, synthesis and biological evaluation of brain targeting l-ascorbic acid prodrugs of ibuprofen with "lock-in" function.

Author information

1
Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
2
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
3
Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China. Electronic address: wyong@scu.edu.cn.

Abstract

A novel brain targeting l-ascorbic acid derivatives with "lock-in" function were designed and synthesized as prodrugs to achieve the effective delivery of ibuprofen to brain by glucose transporter 1 (GLUT1) and the Na(+)-dependent vitamin C transporter SVCT2. Ibuprofen-loaded four prodrugs were tested in the animals. Results from the in vivo distribution study after i.v. administration of these four prodrugs and naked ibuprofen indicated that four prodrugs exhibited excellent transport ability across the BBB and significantly increased the level of ibuprofen in brain. Among them, prodrugs 4 showed higher brain concentration. Both biodistribution data and pharmacokinetic parameters suggested that l-ascorbic acid thiamine disulfide delivery system was a promising carrier to enhance CNS drug's delivery ability into brain.

KEYWORDS:

Brain targeting; Ibuprofen; Prodrugs; Synthesis; Thiamine disulfide; l-Ascorbic acid

PMID:
24927052
DOI:
10.1016/j.ejmech.2014.05.072
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center