A liposome–hydrogel composite ameliorates UVB-induced mouse skin photoaging through integrated antioxidant and extracellular matrix remodeling pathways

Skin photoaging, predominantly caused by chronic ultraviolet B (UVB) exposure, is characterized by oxidative stress, collagen degradation, and disruption of the skin barrier. Deer placenta polypeptides (DPP) are rich in bioactive amino acids (AAs); however, their antioxidant and dermo-protective effects remain insufficiently elucidated, and their topical application is limited by enzymatic instability and poor transdermal permeability. To overcome these limitations, we developed a liposome–hydrogel composite delivery system to enhance the stability, skin penetration, and bioactivity of DPP. DPP obtained via enzymatic hydrolysis exhibited a favorable AA profile, free radical–scavenging activity, and a low molecular weight distribution (3–14 kDa). DPP-loaded liposomes (DPP-LIP) demonstrated high encapsulation efficiency, uniform nanosize, and effective preservation of bioactivity. Incorporation of DPP-LIP into a sodium alginate (SA) hydrogel yielded a composite formulation (DPP-LIP-SA) with sustained-release properties and a 2.7-fold enhancement in transdermal permeation. In a UVB-induced photoaging mouse model, topical administration of DPP-LIP-SA markedly alleviated oxidative stress, inflammatory responses, DNA damage, and extracellular matrix degradation. Mechanistically, DPP-LIP-SA treatment activated the Nrf2/HO-1 antioxidant pathway, inhibited TLR4/MyD88/NF-κB-mediated inflammatory signaling, reduced reactive oxygen species accumulation and lipid peroxidation, and restored extracellular matrix homeostasis by promoting collagen synthesis while suppressing MMP-mediated collagen degradation. Collectively, these findings identify DPP as a potent bioactive peptide resource with intrinsic antioxidant and reparative properties and demonstrate that integration of nanocarriers with hydrogel matrices substantially enhances dermal bioavailability. This composite delivery platform shows strong potential as a peptide-based topical strategy for preventing and treating skin photoaging.