Ascorbyl palmitate/hyaluronan-modified poloxamer 407 nanoparticles for the topical delivery of fisetin to counteract UVB-induced skin photoaging: A novel anti-aging formulation

Fisetin (FIS) has recently been the focal point of multiple studies. Yet, its skin delivery has not been fully investigated due to its low aqueous solubility and high lipophilicity. Herein, FIS-loaded Poloxamer 407 (P407) nanoparticles were modified with Ascorbyl Palmitate (AS) and Hyaluronan (HYA), providing a multimodal approach to preventing UVB-induced skin photoaging. Optimal FIS-AS-HYA-P407 nanoparticles demonstrated a particle size of 214.10 ± 0.32 nm with a zeta potential of −16 ± 0.83 mV, a high entrapment efficiency of 95.61 ± 0.52 %, and a sustained release reaching 68.05 ± 3.32 % over 24 h. FT-IR and DSC confirmed the formation of the nanoparticles and the compatibility of the components. FIS-AS-HYA-P407 nanoparticles penetrated the skin with a flux of 9.23 ± 0.59 µg/cm²/h in 8 h. Confocal microscopy proved the skin penetration of the nanoparticles up to 80 µm with high FIS distribution. The nanoparticles were biocompatible due to the lack of irritation and exhibited potent in vitro antioxidant effects, as confirmed by the DPPH assay. The in vivo study on Wistar rats demonstrated the photoprotective ability of FIS-AS-HYA-P407 nanoparticles via reducing TNFα, NF-κB, and MMP9 and elevating SOD and CAT levels, showing remarkable anti-inflammatory, anti-aging, and antioxidant potential. JNK protein expression was reduced in skin samples pretreated with FIS-AS-HYA-P407 nanoparticles compared to FIS suspension, signifying a high photoprotective outcome. The novelty of this work is attributed to the formulation of FIS for the first time with HYA and AS in P407 nanoparticles to counteract UVB skin damage and photoaging.