Rutin (Rut) is a natural flavonol, well-known for its broad-spectrum of therapeutic effects, including antioxidant and antitumoral activities; still, it has a reduced clinical outcome due to its limited solubility in aqueous solutions. To overcome this drawback, this study proposes a novel formulation for rutin as a proniosomal gel for cutaneous applications. The gel was prepared by coacervation phase-separation method and complies with the standard requirements in terms of particle size (140.5 ± 2.56 nm), zeta potential (−27.33 ± 0.09 mV), encapsulation capacity (> 50%), pH (7.002 ± 0.18) and rheological properties. The results showed high biocompatibility of the gel on the 3D reconstructed human epidermis model characterized by increased viability of the cells and a lack of irritant and phototoxic potential. The evaluations on 2D cells confirm the preferential cytotoxic effect of Rut on melanoma cells (IC₅₀ value = 8.601 µM, nuclear fragmentation) compared to normal keratinocytes. Our data suggest that the proniosomal gel is a promising drug carrier for Rut in the management and prevention of skin disorders.

中文翻译：

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芦丁局部给药的前代体凝胶：使用3D重构的人表皮组织和2D细胞的制备，理化特性和体外毒理学概况

芦丁（Rut）是一种天然的黄酮醇，以广谱的治疗作用而闻名，包括抗氧化和抗肿瘤活性。然而，由于其在水溶液中的有限溶解性，其临床结果有所降低。为了克服这个缺点，本研究提出了一种新的芦丁制剂，作为皮肤应用中的前体凝胶。该凝胶是通过凝聚相分离法制备的，并且在粒度（140.5±2.56 nm），ζ电位（-27.33±0.09 mV），包封容量（> 50％），pH（7.002± 0.18）和流变性。结果表明，该凝胶在3D重建的人类表皮模型上具有很高的生物相容性，其特征在于细胞活力增强，并且缺乏刺激性和光毒性。₅₀值= 8.601 µM，核碎裂）与正常角质形成细胞相比。我们的数据表明，前胎蛋白凝胶是Rut在管理和预防皮肤疾病中很有希望的药物载体。