Harnessing liposomal delivery to boost polyphenols’ potential in chronic wound therapy
Chronic 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. In 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. In 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.