Marine Polysaccharide-Based Microneedles Loaded with TA@CuS Nanoparticles for Efficient Transdermal Antibacterial Therapy of Infected Wounds

Qingdao Key Laboratory of Biomacromolecular Drug Discovery and Development, State Key Laboratory Base of Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China

^* Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it. (Xiangyan Chen); This email address is being protected from spambots. You need JavaScript enabled to view it. (Yantao Li)

Abstract

The treatment of infected wounds faces multiple challenges, including bacterial infection, inflammatory response, delayed tissue repair, and low drug delivery efficiency. Traditional dressings and antibiotic therapies are increasingly inadequate to meet clinical needs due to the emergence of drug-resistant bacterial strains and the difficulty of penetrating the skin barrier. To address these issues, this study developed a soluble microneedle system (TA@CuS-MN) based on a composite matrix of marine-derived chondroitin sulfate (CS) loaded with tannic acid-modified copper sulfide nanoparticles (TA@CuS), enabling synergistic antibacterial effects and localized targeted delivery. Systematic characterization showed that TA@CuS-MN possesses favorable mechanical strength and transdermal delivery capability, allowing sustained local delivery of the nanoparticles. In vitro antibacterial assays demonstrated efficient antibacterial activity against Staphylococcus aureus; biosafety evaluation revealed no significant hemolytic response or cytotoxicity, indicating good biocompatibility. Furthermore, TA@CuS-MN effectively scavenged intracellular reactive oxygen species and promoted tube formation in human umbilical vein endothelial cells, suggesting its potential to promote angiogenesis. This study highlights the synergistic mechanism between marine polysaccharide matrices and polyphenol-modified nanoparticles, offering a new strategy with clinical translation potential for the treatment of complicated wounds infected with drug-resistant bacteria.