Nanostructured Dual-Delivery System with Antioxidant and Synergistic Approach for Targeted Dermal Treatment

Biocompatible nanofibrous dressings integrating bioactive compounds with antioxidative and antimicrobial properties offer a promising solution for effective wound healing. In the presented study, we developed a novel dual-delivery system by combining forcespun nanofibres with poly(3-hydroxybutyrate) (PHB)-liposomes to enhance bioavailability and enable targeted release of bioactive agents (eugenol, thymol, curcumin, ampicillin, streptomycin, gentamicin). These agents exhibited notable antioxidant activity (2.27-2.33 mmol TE/g) and synergistic or partially synergistic antimicrobial effects against <i>E. coli</i>, <i>M. luteus</i>, <i>S. epidermidis</i>, and <i>P. aeruginosa</i> ( Fractional Inhibitory Concentration index 0.09-0.73). The most potent combinations, particularly thymol, eugenol, and ampicillin, were encapsulated in the nanofibre-liposomal matrix. The successful preparation of a new combined delivery system was confirmed by structural analysis using Electron and Fluorescence Microscopy. The dual-composite materials retained the antimicrobial properties of the individual compounds upon release, with the highest increases of ~73.56% against <i>S. epidermidis</i>. Cell viability and in vitro immunology assays using the human keratinocyte cell line (HaCaT) showed a slight decrease in viability and immune response stimulation, while not impairing wound re-epithelisation. These findings highlight the potential of firstly reported novel carrier utilising both PHB-nanofibres and PHB-liposomes, exhibiting simultaneous antioxidant and antimicrobial activity as promising candidates for the treatment of infected wounds under oxidative stress.