张国立, 肖志美, 王秀, 于翔, 方荣震, 杜丽娜, 金义光. 治疗原发性肺癌的共轭亚油酸粉雾剂研究J. 药学学报, 2021,56(10): 2650-2657. doi: 10.16438/j.0513-4870.2021-0492
引用本文: 张国立, 肖志美, 王秀, 于翔, 方荣震, 杜丽娜, 金义光. 治疗原发性肺癌的共轭亚油酸粉雾剂研究J. 药学学报, 2021,56(10): 2650-2657. doi: 10.16438/j.0513-4870.2021-0492
ZHANG Guo-li, XIAO Zhi-mei, WANG Xiu, YU Xiang, FANG Rong-zhen, DU Li-na, JIN Yi-guang. Dry powder inhalers of conjugated linoleic acid for the treatment of primary lung cancerJ. Acta Pharmaceutica Sinica, 2021,56(10): 2650-2657. doi: 10.16438/j.0513-4870.2021-0492
Citation: ZHANG Guo-li, XIAO Zhi-mei, WANG Xiu, YU Xiang, FANG Rong-zhen, DU Li-na, JIN Yi-guang. Dry powder inhalers of conjugated linoleic acid for the treatment of primary lung cancerJ. Acta Pharmaceutica Sinica, 2021,56(10): 2650-2657. doi: 10.16438/j.0513-4870.2021-0492

治疗原发性肺癌的共轭亚油酸粉雾剂研究

Dry powder inhalers of conjugated linoleic acid for the treatment of primary lung cancer

  • 摘要: 共轭亚油酸(conjugated linoleic acid,CLA)是存在于人和动物体内的营养物质,具有抗肿瘤、抗动脉粥样硬化和调节免疫等功能,但其口服生物利用度低。本文制备了CLA粉雾剂(conjugated linoleic acid dry powder inhalers,CDPIs),经大鼠气管给药后治疗大鼠原发性肺癌。首先,制备CLA纳米乳,加入10%甘露醇冻干后得到CDPIs疏松白色粉末,其空气动力学粒径(aerodynamic median diameter,Da)为3.10 μm,适合肺吸入给药。用3-甲基胆蒽及NN-二甲基亚硝胺经气管喷入大鼠肺中,45天后得到原发性肺癌模型。所有动物实验经军事科学院军事医学研究院伦理委员会批准且实验均按照相关指导原则和规定进行。分别将CDPIs、吉非替尼混悬液和空白粉雾剂经气管喷入肺癌大鼠肺中。与模型组比较,吉非替尼混悬液组和CDPIs组的肿瘤结节和炎性细胞数量均明显减少,其中CDPIs组的药效优于吉非替尼混悬液组。CDPIs组CD31和NF-κB p65表达明显减少,优于吉非替尼混悬液组;CDPIs组血管内皮生长因子(vascular endothelial growth factor,VEGF)水平明显降低,与吉非替尼组治疗效果相当;CDPIs组Tunel检测表明细胞凋亡明显增多,明显优于吉非替尼混悬液组。CDPIs能直接将具有优良药理活性的药物递送至肺部肿瘤,是一种具有前景的用于肺癌治疗的肺吸入给药剂型。

     

    Abstract: Conjugated linoleic acid (CLA) is a nutrient substance that exists in humans and animals. It has anti-tumor, anti-atherosclerosis, and immune-regulating functions, but its oral bioavailability is low. Conjugated linoleic acid dry powder inhalers (CDPIs) were prepared and intratracheally administered to the rats that suffered from primary lung cancer. Conjugated linoleic acid nanoemulsions were prepared first and CDPIs were with 10% mannitol after lyophilization. CDPIs are loose white powders with the aerodynamic median diameter (Da) of 3.10 μm, which were suitable for pulmonary delivery. Rats lung cancer models were established after 45 days by instilling 3-methylcholanthrene (MCA) and N,N-dimethylnitrosamine (DEN) into the rats lung once. The animal experiments were approved by the Ethics Committee of Academy of Military Medical Sciences and conducted in accordance with the relevant guidelines and regulations. The CDPIs, gefitinib suspension and blank DPIs were sprayed into the lungs of rats with lung cancer through the trachea. Compared with the model group, both the gefitinib suspension group and the CDPIs group showed significantly fewer tumor nodules and inflammatory cells, and the CDPIs group was better than the gefitinib suspension group. The inhibition efficiency of CDPIs on CD31 and NF-κB p65 was better than that of the gefitinib suspension group. The vascular endothelial growth factor (VEGF) level in the CDPIs group was significantly reduced, which was equivalent to that of the gefitinib suspension group. The apoptosis in the CDPIs group by Tunel tests showed a significant increase, which was significantly better than the gefitinib suspension group. Therefore, CDPIs had excellent pharmacological activity on lung cancer, which provided a model for the efficient delivery of oil therapeutic agents.

     

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