Development of rutin-loaded cerosomes for topical photoprotection and skin barrier modulation

Xeroderma pigmentosum (XP) is a rare DNA-repair disorder associated with extreme photosensitivity, high skin cancer risk, progressive xerosis and barrier dysfunction. Current management relies largely on strict photoprotection, which does not address impaired hydration and epidermal barrier integrity. This work developed cerosomes (ceramide-containing vesicular systems) as multifunctional topical carriers combining barrier-replenishing ceramides with rutin as an antioxidant/photoprotective agent. Box-Behnken design was applied to optimize rutin-loaded cerosomes by evaluating phospholipid concentration, Tween®80:phospholipid ratio and ceramide concentration on the physicochemical properties. The optimized Tween® 80 formulation showed suitable attributes for topical delivery, with vesicle size <300 nm, polydispersity index <0.3, zeta potential <-30 mV, association efficiency >50% and loading capacity ∼0.8% but these were not maintained after 30 days at room-temperature. Surfactant substitution with Pluronic® F-127 or sodium deoxycholate improved storage stability up to 60 days, while rutin release was complete within 6 h and followed Fickian diffusion. In HaCaT keratinocytes, rutin-loaded cerosomes were cytocompatible up to 50-100 μM, while unloaded systems were more cytotoxic, suggesting a protective role of rutin. In vitro photoprotection assays showed that Pluronic®-stabilized cerosomes increased SPF to 40 vs 25 obtained with blank sunscreen, and improved photostability up to 60 min of simulated UV exposure. Barrier-related performance was supported by film-forming/occlusive effects, as well as modulation of water loss and theophylline permeation across artificial membranes and intact/damaged skin models. These findings support rutin-loaded cerosomes as a promising nanoplatform for combined photoprotection and barrier-oriented care in XP.