Targeted delivery of Naringenin-enriched mannosylated niosomal nanogel for effective therapy of skin cancer.

Skin cancer is caused by excessive UVR exposure, which poses a serious health risk. The use of phytoconstituents as medicaments for the management of various diseases has been trending in recent years due to their fewer adverse effects than synthetic medicines. Naringenin (NG) is a natural polyphenol and a potent antioxidant, with remarkable ROS-scavenging and UVR-protection potential. However, NG exhibits limitations in bioavailability, permeability, stability and half-life. We address this drawback with a novel approach to formulate NG-loaded niosomes as a ligand-specific nanocarrier system. A modified thin-film hydration technique and a Box-Behnken experimental design were used to formulate and optimise NG-loaded niosomes (NG-Nio), respectively. The optimised NG-Nio and Mn-NG-Nio formulations were further characterised for vesicular size, ZP, DE, DL and mannose content. Furthermore, the incorporation of Mn-NG-Nio into a topical gel formulation. The Mn-NG-Nio-gel was characterised for rheological properties, spreadability, in vitro drug release and skin permeation. An in vitro cytotoxicity assay demonstrated higher cellular uptake and significant dose-dependent activity across different cell lines. The in vivo study showed significant reductions in myeloperoxidase levels and in UVB-induced 4-HNE and COX-2 protein levels. The research highlights the potential of Mn-NG-Nio for targeting skin cancer cells, reducing UVB-induced inflammation and oxidative stress.