Hyaluronic Acid–Phospholipid Hybrid Nanocarriers (Hyalutocosomes) for Enhanced Dermal Delivery of Vitamin E and Photoprotection

Ultraviolet (UV) radiation drives oxidative stress, inflammation, and collagen degradation, making efficient dermal delivery of antioxidants a key challenge in skin nanobiotechnology. In this study, we developed vitamin E (α-tocopherol)–loaded hyalutocosomes, a hyaluronic acid–decorated deformable phospholipid vesicle system related to previously reported hyalurosomes, and incorporated them into a collagen/vitamin C nanogel to enhance cutaneous penetration and retention. The nanocarriers showed a uniform size of about 160 nm with low polydispersity and very high encapsulation efficiency (~ 99%), and electron microscopy confirmed a distinct HA-coated core–shell morphology. In a UVB-irradiated rat model, the hyalutocosomes-loaded nanogel restored antioxidant enzymes (SOD, CAT) from approximately one-fifth toward near-normal levels, reduced UVB-induced elevations of IL-6, TNF-α, and MMP-9, and improved histological features, including epidermal hyperplasia and collagen disorganization, more effectively than free vitamin E or blank gel. Overall, these results indicate that hyalutocosomes, as an HA-vesicle–based nanocarrier integrated within a collagen biomaterial matrix, can enhance the topical bioavailability of lipophilic antioxidants and provide a promising platform for next-generation anti-photoaging interventions.