Dual delivery of chlorogenic acid and mimic of antimicrobial peptide – towards wound treatment

Abstract

Chronic wounds are a major burden, causing both morbidity and mortality in patients, as well as a massive economical strain on health care systems worldwide. These wounds have a high degree of complexity and are often difficult to treat due to the many factors limiting healing, such as inflammation, biofilm formation and bacterial infections. With these typically persistent infections and a rising threat of antibiotic resistance, there is an urgent need for new and effective dermal antimicrobial treatments. One group of novel antibiotics gaining focus in recent years is antimicrobial peptides (AMPs). Utilization of these compounds could be promising for the treatment of skin infections, but for chronic wounds, effective treatment through single target therapeutics is unlikely. The aim of this project was therefore to develop a novel dermal drug delivery system able to both eradicate bacterial skin infections and improve healing in chronic wounds. This was done by combining chlorogenic acid (CGA) and a synthetic mimic of an antimicrobial peptide in a liposome-in-hydrogel formulation with a bioactive polymer. The CGA and AMP were both single- and dual-loaded into liposome vesicles. Testing of relevant properties was done over a 12-week period to assess both stability and the drug delivery systems ability to deliver an effective and safe treatment to the skin. Liposomal suspensions were incorporated in a chitosan hydrogel and characterized over a 12-week period. The novel drug delivery system showed potential of both eradicating infection and increasing healing, but further testing is needed to assure stability, effective drug release, non-toxic effects on host cells and to characterize the antibacterial activity of CGA and the AMP.