Lignin-Based Nanoparticles Loaded with Essential Oils: Potential for Diabetic Foot Infection Management

Essential oils (EOs) play a pivotal role in wound healing as sustainable bioactive agents capable of counteracting infections and enhancing wound healing. Nevertheless, their application remains limited by challenges such as high volatility, photothermal resistance, and a tendency toward oxidative degradation. Encapsulation of EOs offers a promising strategy to overcome these issues by enhancing their chemical stability and solubility, reducing evaporation rates, and preserving the integrity of bioactive components. Additionally, the application of encapsulated EOs enables their controlled and sustained release, thereby enhancing both bioavailability and therapeutic performance. <i>Eucalyptus citriodora</i> EO was investigated, both in its free form or loaded into lignin-based polyelectrolyte complex (PEC) nanoparticles (NPs), representing an innovative and powerful tool against diabetic foot infection (DFI) occurrence. NPs composed of quaternized lignin (QL) and carboxymethyl lignin (CML), electrostatically interacting, and further cross-linked with tannic acid (TA) were able to encase EO at a loading efficiency of 87.05 ± 0.07%. The NPs displayed sizes of around 150-180 nm, a ζ-potential of -18.90 ± 0.71 mV, and a polydispersity index (PdI) of 0.290 ± 0.01. The lignin-based PEC NPs exhibited a release of 17 ± 0.05% for <i>E. citriodora</i> EO during 24 h of <i>in vitro</i> evaluation, while incubated in phosphate-buffered saline (PBS). <i>E. citriodora</i> EO-loaded lignin-based PEC NPs showed antibacterial activity toward reference strains of <i>Staphylococcus aureus</i> and <i>Staphylococcus epidermidis</i> (0.96 ± 0.04 and 1.06 ± 0.06 cm, respectively), as well as antioxidant activity by free-radical scavenging activity via the DPPH method. The free <i>E. citriodora</i> EO exhibited higher cytotoxic effects toward human fibroblast and keratinocyte cell lines when compared to their NP-associated forms. EO loading into lignin-based PEC NPs significantly reduced its harmful effects on the eukaryotic cells, demonstrating the safety impact of these NP formulations. Overall, this study enhances the potential of lignin-based PEC NPs, loaded with <i>E. citriodora</i> EO as an efficient tool to kill relevant Gram-positive bacteria present in DFIs, yet exert antioxidant and cytocompatibility effects, thereby aiding in the wound healing process.