Inhalable microspheres embedding chitosan-coated PLGA nanoparticles for 2-methoxyestradiol
【作者】 XinHong Guo, XinXin Zhang, Ling Ye, Ying Zhang, Rui Ding, YongWei Hao, YaLin Zhao, ZhenZhong Zhang, Yun Zhang
【期刊名】 Journal of Drug Targeting
【影响因子】 2014年: 2.72
【作者单位】School of Pharmaceutical Sciences,Zhengzhou University,100 Kexue Avenue, Zhengzhou 450001, People’s Republic of China
【年，卷(期)：页码】2014, 22(5):421-427
【关键词】 Cytotoxicity, fine particle fraction, in vivo, inflammation, local lung delivery, spray-drying
【摘要】 Developing a highly effective and lung-targeted local drug delivery carrier with low irritancy may be critical for improving treatment of lung cancer. Using soluble excipients as microspheres (MS) matrix, respirable MS embedding chitosan-coated poly(D,L-lactide-co-glycolide) nanoparticles (CNP-MS) for 2-methoxyestradiol (2-ME) were designed, which could avoid macrophage phagocytosis to achieve the targeted delivery of these drugs. 2-ME CNP-MS were prepared by spray-drying and characterized by morphology, redispersability, fine particle fraction (FPF) and drug release. Cytotoxicity, and lung deposition and histological examination were investigated. Results showed that 2-ME CNP-MS were spherical with a rough surfaces, exhibiting good redispersability, a high respirable fraction and sustained release characteristics. CNP-MS markedly enhanced the cytotoxicity of 2-ME by approximately 8.8-fold and 3.65-fold on SPC-A1 cells compared to solution and NP, respectively. After pulmonary administration, 2-ME CNP were distributed in rat lungs and for 10 mg of 2-ME CNP-MS, haematoxylin and eosin staining showed no obvious difference compared to the untreated control group. Therefore, CNP-MS revealed suitable features for local lung delivery and significantly enhanced cytotoxicity of 2-ME without obvious inflammation in lungs of rats, suggesting that 2-ME CNP-MS have great potential as an inhalation agent for targeted, highly effective and safe treatment of lung cancer.
【全文链接】http://www.sciencedirect.com/science/article/pii/S0939641117304393
