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Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers

机译:脂质体姜黄素干粉吸入器吸入治疗原发性肺癌

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摘要

Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.
机译:肺癌是与癌症相关的死亡的主要原因。传统化学疗法由于这些药物的广泛分布而引起严重的毒性。姜黄素是一种潜在的抗癌药,但其水溶性低,生物利用度差和新陈代谢迅速,严重限制了临床应用。在这里,我们开发了一种脂质体姜黄素干粉吸入器(LCD),用于吸入治疗原发性肺癌。冷冻干燥后,从姜黄素脂质体获得LCD。 LCD的质量平均空气动力学直径为5.81μm,细颗粒率为46.71%,适合于肺部输送。人肺癌A549细胞对姜黄素脂质体的吸收明显大于游离姜黄素。 A549细胞的高细胞毒性和姜黄素脂质体对正常人支气管BEAS-2B上皮细胞的低细胞毒性产生了高选择指数,部分原因是细胞凋亡增加。姜黄素粉,LCD和吉西他滨通过气管直接喷入肺癌大鼠的肺中。 LCD在病理学和许多与癌症相关的标志物(包括VEGF,丙二醛,TNF-α,caspase-3和BCL-2)的表达方面显示出比其他两种药物更高的抗癌作用。 LCD是用于肺癌的吸入治疗的有前途的药物,具有很高的治疗效率。

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