Orange Peel Bioactives for Skin Exposome Defense: A Review of Transferosomal Dermaceuticals Against UV Radiation, Blue Light and Air Pollution

Abstract

The skin exposome represents a multifactorial burden of environmental stressors, including ultraviolet (UV) radiation, high-energy visible (HEV) blue light, and airborne particulate pollution, that collectively contribute to oxidative stress, inflammation, DNA damage, matrix metalloproteinase activation, collagen degradation, pigmentation, and premature skin aging. Sweet-orange peel (Citrus sinensis) contains a diverse profile of flavonoids, phenolics, polymethoxylated flavones, carotenoids, and volatile constituents that have been investigated for several skin-relevant biological activities. However, the limited aqueous solubility, chemical instability, and restricted penetration of several phytochemicals across the stratum corneum may limit their topical effectiveness. Transferosomes, ultra-deformable phospholipid vesicles incorporating edge activators, offer a promising delivery platform by improving vesicular flexibility. This review integrates current evidence concerning skin exposome stressors, orange peel phytochemistry, biological activities relevant to environmental skin damage, and transferosomal drug-delivery strategies. Particular emphasis is placed on the proposed development of an orange peel extract-loaded transferosomal lotion and the potential application of Quality-by-Design and Box–Behnken experimental design for formulation optimization. Although individual components demonstrate promising biological activities, direct evidence for an integrated formulation against combined UV, blue-light, and pollution exposure remains limited. Standardization of botanical extracts, vesicle stability, characterization, scalability, dermal safety, and clinical validation therefore remain important translational challenges. Overall, transferosomal delivery represents a rational approach for converting citrus waste-derived bioactives into sustainable, multifunctional dermaceutical systems targeting the skin exposome.