The present study improved the effectiveness of a poorly water-soluble drug, luteolin (LUT), by encapsulating it in lecithin–bile salt-integrated system called bilosomes (BLs). Such a delivery system offers the benefits of mimicking the skin's biological structure and being a prominent tool to circumvent skin delivery obstacles. The prepared BLs underwent complete in vitro assessment. The developed BLs showed enhanced characteristics compared to free luteolin suspension (P < 0.05). Optimized BLs attained good entrapment efficiency (78.60% ± 0.88%), small particle size (226.1 ± 2.45 nm), and sustained drug-release pattern. The study also showed that both blank and LUT-loaded BLs preparations were safe to the skin with a primary irritancy index of < 2 based on the Draize test. In vivo tests were conducted to study the effect of the bile salt-based nanovesicles compared with the free LUT suspension. The photoprotective effect was evaluated according to the visual examination and biochemical analyses of antioxidant, anti-inflammatory, and anti-wrinkling markers after ultraviolet B irradiation. Results of biochemical markers and histopathological examination demonstrated that the LUT-BLs effect was superior than the LUT suspension (P < 0.05). Consequently, the current study proves that novel LUT-loaded BLs is a promising nanoplatform that overcome LUT delivery obstacles and, hence, alleviate UV-induced skin damage.
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