深度共晶溶剂辅助山奈酚水凝胶的开发:一种治疗银屑病样皮肤炎症的有前景的方法。
Development of a Deep Eutectic Solvent-Assisted Kaempferol Hydrogel: A Promising Therapeutic Approach for Psoriasis-like Skin Inflammation.
发表日期:2023 Oct 30
作者:
Huining Su, Zhicheng Liu, Zuoliang Zhang, Xunan Jing, Lingjie Meng
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
牛皮癣是一种无法治愈的炎症性皮肤病,由免疫系统介导。尽管山奈酚以其抗炎、抗氧化和抗癌特性而闻名,但由于其水溶性差和生物利用度低,其治疗效果往往受到限制。为了应对这些挑战,我们使用 Pluronic F127 和含有不同浓度山奈酚的低共熔溶剂 (DES) 开发了一种有前途的山奈酚水凝胶 (DK-pGEL)。在本研究中,我们首先评估了 DK-pGEL 水凝胶的流变特性和粘度。 37°C 时,DK-pGEL (~14 kPa) 水凝胶的 G' 显着低于对照组 (~30 kPa)。 DK-pGEL 水凝胶在 37 °C 时表现出理想的流动性和粘度,其剪切稀化行为证明了这一点。此外,DK-pGEL 水凝胶表现出控释特性,60 小时内药物释放量为 97.43 ± 5.37 μg/mL。此外,体外抗氧化实验表明,DK-pGEL 对 DPPH 自由基 (96.27 ± 0.37%)、ABTS 自由基 (98.11 ± 0.79%)、羟基自由基 (66.36 ± 1.01%) 和超氧化物表现出显着的自由基清除能力。 -浓度为 250 μg/mL 山奈酚时的自由基 (90.52 ± 0.79%)。此外,DK-pGEL 通过抑制活性氧的产生而表现出显着的细胞抗氧化作用。进行细胞活力测定 (CCK8) 和活/死细胞测定来评估 DK-pGEL 的细胞毒性。结果表明,DK-pGEL能够有效抑制HaCaT细胞增殖,且不会引起明显的细胞毒性。为了评估 DK-pGEL 的治疗潜力,采用了咪喹莫特 (IMQ) 诱导的银屑病样病变小鼠模型。值得注意的是,DK-pGEL 水凝胶可以显着减少银屑病面积和严重程度指数评分,改善 IMQ 诱导的组织病理学,并下调银屑病中促炎细胞因子(TNF-α、IL-6 和 IL-17A)的表达。皮肤组织。这些发现表明,DES 辅助的山奈酚水凝胶有望作为治疗牛皮癣的局部药物递送系统。
Psoriasis is an incurable inflammatory skin disease that is mediated by the immune system. Although kaempferol has been known for its anti-inflammatory, antioxidant, and anticancer properties, its therapeutic effectiveness is often limited due to its poor water solubility and low bioavailability. To address these challenges, we developed a promising kaempferol hydrogel (DK-pGEL) using Pluronic F127 and a deep eutectic solvent (DES) with varying concentrations of kaempferol. In this study, we first evaluated the rheological properties and viscosity of the DK-pGEL hydrogel. The G' of DK-pGEL (∼14 kPa) hydrogels was significantly lower than the control group (∼30 kPa) at 37 °C. The DK-pGEL hydrogel exhibited ideal fluidity and viscosity at 37 °C, as demonstrated by its shear-thinning behavior. Moreover, the DK-pGEL hydrogel showed controlled release characteristics with a drug release of 97.43 ± 5.37 μg/mL over 60 h. Furthermore, in vitro antioxidant experiments revealed that DK-pGEL exhibited significant radical scavenging ability against the DPPH-radical (96.27 ± 0.37%), ABTS-radical (98.11 ± 0.79%), hydroxyl-radical (66.36 ± 1.01%), and superoxide-radical (90.52 ± 0.79%) at a concentration of 250 μg/mL kaempferol. Additionally, DK-pGEL exhibited notable cellular antioxidant effects by inhibiting reactive oxygen species generation. Cell viability assays (CCK8) and live/dead cell assays were conducted to assess the cytotoxicity of DK-pGEL. The results showed that DK-pGEL could effectively inhibit HaCaT cell proliferation without causing significant cytotoxicity. To evaluate the therapeutic potential of DK-pGEL, an imiquimod (IMQ)-induced mouse model of psoriasis-like lesions was employed. Remarkably, the DK-pGEL hydrogel could significantly reduce the psoriasis area and severity index score, improve the histopathology induced by IMQ, and downregulate the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-17A) in the skin tissue. These findings demonstrate that the DES-assisted kaempferol hydrogel holds promise as a topical drug delivery system for psoriasis treatment.