Understanding the effects of TCP-25 and EDTA interaction : A study of the biophysical aspects of a naturally derived peptide formulation with EDTA for topical application

Sammanfattning: Chronic wounds are an emerging healthcare issue and current methods of healing chronic wounds address bacteria but are ineffective against resistant bacteria and the biofilm formation commonly observed in these wounds. Antimicrobial peptides (AMPs) derived from the endogenous wound healing system have been shown to combat bacterial infections, exhibit immunomodulatory effects, as well as improving wound healing. A 25 amino acid AMP derived from the C-terminal region of thrombin (TCP-25) have been thoroughly investigated by the Xinnate group. This peptide has proven successful antimicrobial and anti-inflammatory activity both in vitro and in vivo studies conducted on chronic wounds. As a result, the peptide has been formulated into a gel and is currently undergoing a first-in-human clinical safety study. To improve the current formulation, efforts are made to develop a formulation able to effectively defeat biofilms. Specifically, a formulation incorporating EDTA has been investigated. Preliminary studies have shown the EDTA enhances the bactericidal activity of TCP-25. Biophysical properties studied during this project indicated that EDTA did not impact the peptide structure or LPS binding. More importantly, EDTA addition was found to have a positive impact on the peptide stability at RT, which could be related to increased oligomerization observed during thermal denaturation studies. In summary, the study suggests that the addition of EDTA improves the formulation, thereby highlighting its potential as a promising strategy for developing a new gel containing TCP-25 as active ingredient.