School of Pharmacy , Anhui University of Chinese Medicine , Hefei 230012 , P. R. China.
Institute of Pharmaceutics , Anhui Academy of Chinese Medicine , Hefei 230012 , P. R. China.
Mol Pharm. 2018 May 7;15(5):2007-2016. doi: 10.1021/acs.molpharmaceut.8b00161. Epub 2018 Apr 17.
Lung cancer is a kind of malignant tumor with high morbidity and metastasis tendency. Gambogic acid (GA) has demonstrated significant antitumor activity in vitro, but its poor water-solubility and adverse effects restrict its application in vivo and in clinic. In this study, a passive-targeting GA delivery system was prepared for orthotopic Lewis lung carcinoma model mice. Besides the ∼7 μm size distribution, slow and steady in vitro drug release in a week, high targeting effect to lung, effective restoration of histomorphological abnormalities in lung, maintaining on bodyweight, and prolongation on survival time, excellent improvements of the GA-loaded particles on physiological and psychological statuses and obvious inhibition on tumor metastasis to liver have also been observed, through the measurements of Porsolt forced swim, hypoxic tolerance time, ultrastructure of pulmonary capillary, pulmonary vascular permeability, and hepatic histological change. These results suggest that this GA-loaded particle may be an ideal approach to achieve satisfactory therapeutic function on lung cancer.
肺癌是一种发病率和转移倾向都很高的恶性肿瘤。藤黄酸(GA)在体外具有显著的抗肿瘤活性,但由于其水溶性差和不良反应,限制了其在体内和临床的应用。本研究制备了一种被动靶向 GA 递药系统,用于荷 Lewis 肺癌模型小鼠。除了约 7μm 的粒径分布、体外一周内缓慢且稳定的药物释放、对肺的高靶向作用、有效恢复肺组织形态学异常、维持体重和延长生存时间外,还通过强迫游泳、低氧耐受时间、肺毛细血管超微结构、肺血管通透性和肝组织学变化的测量,观察到载 GA 粒子对生理和心理状态的显著改善,以及对肿瘤转移到肝脏的明显抑制作用。这些结果表明,该载 GA 粒子可能是实现肺癌令人满意治疗效果的理想方法。