Affordable Access

Publisher Website

Vitamin C and 6-amino-vitamin C conjugates of diclofenac: synthesis and evaluation

Authors
Journal
International Journal of Pharmaceutics
0378-5173
Publisher
Elsevier
Publication Date
Volume
291
Identifiers
DOI: 10.1016/j.ijpharm.2004.07.054
Keywords
  • Diclofenac
  • Ascorbic Acid
  • Pro-Drug
  • Svct2
  • Synthesis
  • Stability
Disciplines
  • Biology

Abstract

Abstract Diclofenac (Diclo), its ascorbic acid (AA) or 6-amino-AA (AA-NH 2) pro-drugs (AA-Diclo or AA-NH-Diclo) were prepared and evaluated on human retinal pigment epithelium (HRPE) cells to investigate their ability to interact with the vitamin C transporter SVCT2 and their cellular uptake. Furthermore, stabilities in physiological fluids of these compounds were investigated. For kinetic experiments, AA-Diclo was incubated in Tris–HCl buffer, human plasma or whole blood. The extracted samples were analysed by HPLC. AA-Diclo was hydrolysed following first order kinetics in buffer, plasma ( t 1/2 about 10 h) and whole blood ( t 1/2 about 3.5 h). Transport and inhibition assays were performed by adding [ 14C]AA and the above-mentioned unlabelled compounds to plated HRPE cells. Intracellular accumulation was measured incubating HRPE cells with increasing concentrations of unlabelled compounds, following by HPLC analysis. Diclo resulted as a non-competitive inhibitor of AA-transport, showing a Na +-dependent and ascorbate-independent uptake. AA-Diclo behaved as a competitive inhibitor, but it was not transported into cells, whereas its analogue AA-NH-Diclo showed a decreased inhibitory activity. Stability studies suggest AA-Diclo as a potential candidate to enhance the Diclo short half life in vivo. The discovery of a Na +-dependent transporter for Diclo on HRPE cells opens new perspectives for targeting diclofenac into the brain.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments

More articles like this

Vitamin C and 6-amino-vitamin C conjugates of dicl...

on International Journal of Pharm... Mar 03, 2005

Diastereoselective synthesis of C60/steroid conjug...

on The Journal of Organic Chemist... Apr 05, 2013

Semi-rigidN-para-ferrocenyl(benzoyl)amino-acid est...

on Inorganic Chemistry Communicat... Jan 01, 2002
More articles like this..