Topical cream loaded with upcycled citrus bioactive chitosan-pectin nanoparticle protects skin from UV-induced photoaging.

Photoaging, driven by chronic ultraviolet (UV) exposure, accelerates skin aging through inflammation, collagen degradation, and oxidative stress. This study presents a novel and sustainable anti-photoaging formulation, Nano Citrus Cream (NCC), based on chitosan-pectin (CHI-PEC) nanoparticles loaded with a polyphenol-rich grapefruit extract and orange essential oil. The optimized nanoparticles (CH-PEC, 1:1) exhibited high encapsulation efficiency (up to 87.9%), nanoscale size (49-101 nm), and colloidal stability (+30 to +54 mV). When incorporated into a topical cream, NCC showed shear-thinning rheology, controlled polyphenols release, and was well-tolerated in vivo. In a UVB-induced photoaging rat model, NCC significantly reduced erythema, scaling, and histopathological alterations, outperforming non-encapsulated extract treatments. Biochemical analyses demonstrated downregulation of MMP3, TSP1, and LMN332, key markers associated with extracellular matrix degradation, inflammation, and basement membrane disruption. LC-ESI-HRMS profiling identified 71 bioactive compounds from phenolic, lipid-derived and terpenoid classes, several of which exhibited favorable predicted skin permeability. Molecular docking was applied as an exploratory, hypothesis-generating tool to assess potential interactions between selected skin-permeable metabolites and photoaging-realted enzymes, without assigning compound-specific dominance. Overall, the results support a nano-enable, multicomponent mode of action underlying the anti-photoaging efficacy of NCC. This work highlights NCC as a safe, biodegradable, and sustainable cosmetic formulation, while demonstrating the potential of nanotechnology-based delivery systems for valorizing citrus by-products in skin health applications.