Enhanced wound healing activity of naturally derived Lagenaria siceraria seed oil binary nanoethosomal gel: formulation, characterization, in vitro/in vivo efficiency

Abstract Background The present study aims to enhance the wound healing potential of the seed oil (SO) of Lagenaria siceraria (Egyptian cultivar) via the preparation of SO-loaded binary nanoethosomal (SO-BNE) gels. SO-BNEs were prepared using 2 3 factorial design, characterized for vesicle size, zeta potential, polydispersity index, linoleic and oleic acid EE% for ensuring improved skin permeability. The L. siceraria SO, optimized SO-BNE gels (0.5% and 5%) and Mebo® were topically applied in full-thickness wounded rat model twice daily for 10 days. Results In the SO-BNE gel groups, the normal appearance of the skin architecture and structure of the dermis was revealed. In addition, the levels of NRF2, TGF-β1 and FOXO1, collagen type I, SMA-α and MIP2 were significantly elevated. The wound healing potential of SO-BNE gels was proposed to be via suppression of oxidative stress and stimulation of skin regeneration biomarkers. Furthermore, the SO screening through GC/MS unveiled high percentages of unsaturated fatty acids. SO was also found to be nontoxic to human skin fibroblast cells; enhanced viability and migration rates at concentration of 50 g/mL by 99.76% and 75.9%, respectively. Conclusion These findings demonstrate that the Lagenaria siceraria SO-loaded BNE gels represent a promising delivery for wound healing with enhanced release and bioavailability.