A multi-functional microneedle patch loaded with mupirocin and L-arginine nanoparticles for enhancing antibacterial activity, anti-inflammation and diabetic wound healing

Multifunctional microneedles MR-NPs-MNs was developed for chronic wound treatment, loading mupirocin and L-arginine into PLGA nanoparticles. • The MR-NPs-MNs penetrate the stratum corneum, facilitating deep drug delivery and a synergistic antibacterial effect with mupirocin. • Co-encapsulation of mupirocin and L-arginine in MR-NPs synergizes immediate antibacterial action with wound microenvironment remodeling. • MR-NP s-MNs simultaneously address infection, inflammation and tissue repair to accelerate wound healing. Chronic wounds pose notable clinical challenges due to persistent infection, inflammation, and impaired tissue regeneration. We designed a multi-functional microneedle patch (MR-NPs-MNs) comprising chitosan-based microneedles encapsulating PLGA nanoparticles co-loaded with mupirocin and L-arginine. As a key component, L-arginine significantly enhances anti-inflammatory effects by reducing pro-inflammatory cytokines and effectively promotes tissue repair by regulating oxidative stress and facilitating angiogenesis. The PLGA nanoparticles MR-NPs exhibited stable physical properties (181.7 ± 5.875 nm particle size, 22.4 ± 0.529 mV zeta potential) and were incorporated into microneedles capable of withstanding 40.38 N compression. Notably, MR-NPs-MNs outperformed conventional mupirocin ointment, achieving a 99.82 ± 0.15% antibacterial rate (vs. 90.69 ± 1.11% for the ointment), superior biofilm inhibition (96.82 ± 0.83% and 77.8 ± 5.32%), and enhanced transdermal drug delivery. In vitro, MR-NPs-MNs increased NO production, reduced TNF-α, IL-6 and ROS levels, and promoted wound healing. In diabetic wound models, MR-NPs-MNs increased the healing rate by 1.54-fold, significantly reduced bacterial counts ( P  < 0.01) by day 9, and improved key healing parameters including collagen matrix reorganization, robust neovascularization, and functional tissue formation. With its biocompatible components, this system provides a potential local therapeutic platform for infected diabetic wound treatment. Download: Download high-res image (153KB) Download: Download full-size image