Microneedle-Assisted Topical Delivery of Idebenone-Loaded Bioadhesive Nanoparticles Protect against UV-Induced Skin Damage

Ultraviolet (UV) radiation can penetrate the basal layer of the skin and induce profound alterations in the underlying dermal tissues, including skin pigmentation, oxidative stress, photoaging, glycation, and skin cancer. Idebenone (IDB), an effective antioxidant that suppresses melanin biosynthesis and glycation, can protect the skin from UV-induced damage, accounting for its use in commercial anti-aging formulations. Ideally, IDB formulations should retain IDB inside the skin for a sufficient period, despite disturbances such as sweating or swimming. Herein, we present an IDB topical formulation based on Tris (tris(hydroxymethyl)-aminomethane)-modified bioadhesive nanoparticles (Tris-BNPs) and microneedle-assisted delivery. We found that Tris-BNPs loaded with IDB (IDB/Tris-BNPs) effectively reached the basal layer of the skin and were retained for at least 4 days with a slow and continuous drug release profile, unlike non-bioadhesive nanoparticles (NNPs) and bioadhesive nanoparticles (BNPs) of similar sizes (ranging from 120–142 nm) and zeta-potentials (above −20 mV), which experienced a significant reduction in concentration within 24 h. Notably, IDB/Tris-BNPs showed superior performance against UV-induced damage relative to IDB/NNPs and IDB/BNPs. This effect was demonstrated by lower levels of reactive oxygen species and advanced glycation end-products in skin tissues, as well as suppressed melanogenesis. Therefore, the proposed IDB delivery strategy provided long-term protective effects against UV-induced skin damage.