Silver complex of salicylic acid and its hydrogel-cream in wound healing chemotherapy

Abstract

The known metallotherapeutic [Ag(salH)]₂ (AGSAL-1) of salicylic acid (salH₂), was used for the development of new efficient silver based material for wounds healing. AGSAL-1 was characterized by spectroscopic techniques and X-ray crystallography. The wound healing epithelialization of AGSAL-1 was investigated by the means of scratch assay against immortalized human keratinocytes (HaCaT) cells. The anti-inflammatory activity of AGSAL-1 was evaluated by monitoring the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX). The antibacterial activity of AGSAL-1 was evaluated against bacterial species which colonize wounds, such as: Pseudomonas aeruginosa (PAO1), Staphylococcus epidermidis and Staphylococcus aureus, by the means of Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and their Inhibition Zone (IZ). Moreover, the influence of AGSAL-1 against the formation of biofilm of PAO1 and St. aureus was also evaluated by the mean of Biofilm Elimination Concentration (ΒΕC). A hydrogel material CMC@AGSAL-1, based on the dispersion of AGSAL-1 in to carboxymethyl cellulose (CMC) was tested for its antimicrobial activity. Molecular Docking was performed, to explore the molecular interaction of AGSAL-1 with (i) the transcriptional regulator of PAO1, LasR. (ii) the mevalonate pathway for the biosynthesis of isoprenoids which is essential for gram-positive bacteria St. epidermidis and St. aureus. The toxicity of AGSAL-1 was examined against the HaCaT cells. Its genotoxicity was evaluated using Allium cepa model, in vivo. No genotoxicity was detected, indicating that AGSAL-1 is a candidate towards the development on a new efficient medication of the silver based metallodrugs.

Keywords: Anti-inflammatory; Antibacterial; Bioinorganic materials chemistry; Salicylic acid; Silver(I) complexes; Wound healing.