Peptide conjugates of a nonsteroidal anti-inflammatory drug as supramolecular gelators: synthesis, characterization, and biological studies.

Abstract

Indomethacin (IND), which is a well-known nonsteroidal anti-inflammatory drug (NSAID), was conjugated with various naturally occurring amino acids. Most of these bioconjugates were capable of gelling pure water, a solution of NaCl (0.9 wt%), and phosphate-buffered saline (pH 7.4), as well as a few organic solvents. The gels were characterized by table-top and dynamic rheology, and electron microscopy. Variable-temperature (1)H NMR spectroscopy studies on a selected gel were performed to gain insights into the self-assembly process during gel formation. Both 1D and 2D hydrogen-bonded networks were observed in the single-crystal structures of two of the gelators. Plausible biological applications of the hydrogelators were evaluated with the ultimate aim of drug delivery in a self-delivery fashion. All hydrogelators were stable in phosphate-buffered saline at pH 7.4 at 37 °C, and biocompatible in mouse macrophage RAW 264.7 cell line (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay). Two of the most biocompatible hydrogelators displayed an anti-inflammatory response comparable to that of the parent drug IND in prostaglandin E2 assay. Release of the bioconjugates into the bulk solvent interfaced with the corresponding hydrogels indicated their plausible future application in drug delivery.