Thymoquinone-Loaded Electrospun Fibrous Mats as Advanced Wound Dressing Materials

Background: Thymoquinone (TQ), a bioactive compound derived from Nigella sativa L., exhibits promising antioxidant, anti-inflammatory, and wound-healing properties; however, its clinical application is limited by poor solubility and instability. Methods: In this study, three electrospun nanofiber systems based on different polymeric matrices, PVP (N1), PVP/HPβCD (N2), and PVP/PCL (N3), were developed as potential wound dressing materials for controlled TQ delivery. Results: All formulations produced uniform nanofibrous structures with TQ molecularly dispersed within the polymer matrix, as confirmed by SEM, XRPD, and FTIR analyses. The composition of the nanofibers significantly influenced their physicochemical and functional properties. The N2 system, containing hydroxypropyl-β-cyclodextrin (HPβCD), exhibited the smallest fiber diameter (~208 nm), the fastest drug release, and enhanced antioxidant and anti-inflammatory activity due to improved TQ solubility. In contrast, the N3 system, incorporating polycaprolactone (PCL), formed thicker fibers (~1089 nm) and demonstrated sustained release behavior, the highest mucoadhesion, and the most pronounced wound-healing effect (90% closure after 24 h). Stability studies revealed that HPβCD significantly improved TQ resistance to thermal, humidity, and photolytic degradation, whereas the PVP-based system without stabilizers showed the lowest stability. Principal component analysis (PCA) confirmed that nanofiber performance is governed by two key factors: drug availability and sustained release combined with bioadhesion. Importantly, wound-healing efficiency correlated more strongly with the latter. Conclusions: The results demonstrate that rational design of polymer composition enables modulation of TQ delivery and biological response. Among the tested systems, PVP/PCL nanofibers appear to be the most promising candidates for wound-dressing applications due to their ability to provide sustained drug release and enhance tissue regeneration.