Self-assembled Micelle Loading Cabazitaxel for therapy of Lung Cancer

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• 作者：Bo Zhuang^a ; ^c ; ¹ ; Liang Du^b ; ¹ ; Hongxia Xu^d ; Xuelian Xu^a ; Cheng Wang^a ; ^{cheng13980029671@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yingfang Fan^a ; Mengyi Cong^a ; Jiaqi Yin^a ; Hongxia Li^a ; Huashi Guan^a ;
• 关键词：Cabazitaxel (PubChem CID ; 9854073) ; Ethylene glycol (PubChem CID ; 174) ; ε-Caprolactone (PubChem CID ; 10401) ; Stannous octoate (PubChem CID ; 9318)
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：29 February 2016
• 年：2016
• 卷：499
• 期：1-2
• 页码：146-155
• 全文大小：3072 K

文摘

Lung cancer is a leading cause of cancer deaths worldwide, chemotherapy has improved overall survival but remains limited at <12 months median overall survival. Cabazitaxel is hopeful to do the same in advanced lung cancer as well as in metastatic prostate cancer. However, its clinical application was restricted due to its high hydrophobicity and severe side effects. To overcome these problems, we developed self-assembled micelle loading cabazitaxel (CBZ-PM) for therapy of lung cancer. The CBZ-PM has high drug loading (10.52%) and encapsulation efficiency (99.30%) with particle size of 28.77 ± 0.52 nm and polydisperse index of 0.114 ± 0.012. The transmission electron microscope image presented its spherical and homogeneous appearance. In vitro release profile showed CBZ-PM has a sustained-release behavior. Furthermore, the result of cell proliferation assays proved that CBZ-PM could induce the Lewis lung carcinoma (LLC) cells death through G₂/M arrest more effectively than free CBZ. In vivo anti-tumor activity of CBZ-PM was further studied in mice model of LLC. The tumor inhibitory rate of CBZ-PM was more than 50% and the survival time of LLC bearing mice was efficiently prolonged following administration of CBZ-PM. In addition, the immunohistochemical study showed that more apoptosis cells were detected in the tumor tissue of CBZ-PM group than that of the positive control group. All these indicated that CBZ-PM served as a potential anti-lung cancer agent.