维甲酸倍他米松柔性纳米脂质体制备及其对银屑病细胞模型异常增殖的影响

    Preparation of Flexible Nano-liposomes Co-loaded with Trans-retinoic Acid and Betamethasone and Its Effect on Abnormal Proliferation in Psoriatic Cell Model

    • 摘要:
      目的 探讨维甲酸倍他米松柔性纳米脂质体对银屑病细胞模型的联合治疗作用,为维甲酸倍他米松柔性纳米脂质体的制剂开发提供理论依据。
      方法 采用荧光标记技术(ODA-FITC示踪法)系统评估柔性纳米脂质体的细胞摄取效率及透皮递药性能;采用人角质形成细胞生长刺激因子(keratinocyte growth stimulating factor,KGF)诱导HaCaT细胞建立银屑病异常增殖细胞模型;采用MTT法以OD值为指标考察维甲酸倍他米松柔性纳米脂质体对细胞模型异常增殖的影响;采用酶联免疫法检测炎症因子的变化。
      结果 柔性纳米脂质体在HaCaT细胞上的摄取具有一定的时间依赖性,具有良好的经皮渗透性,KGF刺激HaCaT细胞24 h,浓度选择80 ng·mL−1可建立银屑病异常增殖细胞模型。 维甲酸倍他米松柔性纳米脂质体溶液可显著抑制HaCaT银屑病细胞模型的异常增殖,酶联免疫试验表明其可显著降低TNF-α及IL-6的分泌,所有结果显示两药联用优于单药组,柔性纳米脂质体组优于游离药物组。
      结论 维甲酸倍他米松柔性纳米脂质体能够被角质形成细胞高效摄取,并展现出优异的经皮渗透性。它通过抑制角质形成细胞的异常增殖,同时减少TNF-α、IL-6等炎症因子的分泌,从而发挥联合治疗银屑病的作用。

       

      Abstract:
      OBJECTIVE To investigate the synergistic therapeutic effect of flexible nano-liposomes co-loaded with trans-retinoic acid and betamethasone(TRA-BT-FNL) in psoriasis cell model, and to provide a theoretical basis for the development of TRA-BT-FNL.
      METHODS Used fluorescence labeling technology(ODA-FITC tracing method) to systematic evaluate cellular uptake efficiency and transdermal drug delivery performance of flexible nano-liposomes; used keratinocyte growth stimulating factor(KGF) to induce HaCaT cells to establish a psoriasis abnormal proliferation cell model; used MTT method with OD value as an indicator to investigate the effect of TRA-BT-FNL on the abnormal proliferation of cell models; enzyme-linked immunoassay(ELISA) was used to detect the changes of inflammatory factors.
      RESULTS The uptake of flexible nano-liposomes on HaCaT cells was time-dependent and had good transdermal permeability. KGF stimulated HaCaT cells for 24 h, and the concentration of 80 ng·mL−1 could establish a model of abnormal proliferation of psoriasis. TRA-BT-FNL could significantly inhibit the abnormal proliferation of HaCaT psoriasis cell model, and ELISA showed that it could significantly reduce the secretion of TNF-α and IL-6. All the results showed that the combination of two drugs was superior to the single drug group, and the flexible nano-liposome group was superior to the free drug group.
      CONCLUSION TRA-BT-FNL can be ingestioned by keratinocyte better, which has good percutaneous permeability, it can inhibit the abnormal proliferation of keratinocytes and expression of the inflammatory factors such as TNF-α, IL-6, which play an important role in the treatment of psoriasis.

       

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