AUTHOR=Hemmingsen Lisa Myrseth , Kristensen Marte , Dang Cecilie Thanh Loan , Salamonsen Mari , Fredheim Elizabeth G. Aarag , Škalko-Basnet Nataša 
  
TITLE=Harnessing liposomal delivery to boost polyphenols’ potential in chronic wound therapy
  
JOURNAL=Frontiers in Drug Delivery
  
VOLUME=Volume 6 - 2026
  
YEAR=2026
  
URL=https://www.frontiersin.org/journals/drug-delivery/articles/10.3389/fddev.2026.1839747
  
DOI=10.3389/fddev.2026.1839747
  
ISSN=2674-0850
  
ABSTRACT=IntroductionChronic wounds pose a significant clinical challenge due to impaired healing, persistent inflammation, and susceptibility to infection, often by antimicrobial-resistant bacteria. Therefore, active compounds should ideally act both as antimicrobials with limited potential for resistance development and offer other beneficial wound-healing properties. Polyphenols, such as chlorogenic acid (CGA) and quercetin (QCT), exhibit those properties, but are limited by poor stability or low bioavailability.MethodsIn this study, liposomal formulations of CGA (CGA-LP) and QCT (QCT-LP) were tailored to overcome delivery barriers to wound sites. Liposomes were characterized by size, size distribution, zeta potential, entrapment efficiency, and stability.Results and DiscussionIn vitro release studies for CGA-LP and QCT-LP demonstrated sustained payload release of ∼30% and ∼50%, respectively, over 24 h. Antioxidant activity of both compounds was assessed using DPPH and ABTS·+ assays, confirming the radical scavenging potential of CGA comparable to vitamins C and E, while QCT showed high DPPH activity, but limited ABTS·+ activity. Biocompatibility studies on murine macrophages revealed no cytotoxicity for either formulation. Antibacterial activity was assessed via broth microdilution for both formulations and isothermal microcalorimetry for CGA-LPs. Only QCT-LP potent measurable inhibitory effects against Staphylococcus aureus in the broth microdilution assay; however, effects on metabolic activity were observed for CGA-LPs. These findings suggest that liposomal entrapment could protect polyphenols and prolong or tailor their release, potentially offering a promising strategy for chronic wound therapy and addressing challenges associated with oxidative stress and bacterial infections.