Wu ZhouXue, Zou XiaoYan, Yang LingLin, Lin Sheng, Fan Juan, Yang Bo, Sun XiaoYang, Wan Qiang, Chen Yue, Fu ShaoZhi
Department of Clinical Medicine, Xiangya School of Medicine, Central South University, Changsha, China.
Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China.
Colloids Surf B Biointerfaces. 2014 Oct 1;122:90-98. doi: 10.1016/j.colsurfb.2014.06.052. Epub 2014 Jul 1.
In this study, an in situ gel-based dual drug delivery system (PEG-PCL-PEG/DDP+MPEG-PCL/PTX, abbreviated as PDMP) was prepared through the combination of a cisplatin (DDP)-containing thermosensitive hydrogel (PEG-PCL-PEG/DDP, PECE/DDP) and paclitaxel (PTX)-loaded polymeric micelles (average diameter of 20.1nm). PDMP is a free-flowing solution at room temperature and forms a stationary gel at body temperature, allowing it to serve as a drug depot for the in situ treatment of lung cancer. For in vivo experiments, the xenografted lung cancer model was used to evaluate the anti-tumor efficacy of the PDMP. The results suggested that PDMP is effective at inhibiting tumor growth and prolonging the survival time of tumor-bearing BALB/c nude mice. The survival time of the PDMP-treated group (53 days) is significantly higher than that of other groups (40 days from the free DDP+PTX group, 26 days from the blank PECE group, 25 days from the normal saline group, p<0.05). Immunohistochemical analysis revealed that tumors in the PDMP group had fewer microvessels and lower proliferation activity compared with those of the control group. Thus, PDMP may have great potential for in situ treatment of lung cancer by minimally invasive injection methods.
在本研究中,通过将含顺铂(DDP)的热敏水凝胶(PEG-PCL-PEG/DDP,PECE/DDP)与载有紫杉醇(PTX)的聚合物胶束(平均直径20.1nm)相结合,制备了一种基于原位凝胶的双药递送系统(PEG-PCL-PEG/DDP+MPEG-PCL/PTX,简称为PDMP)。PDMP在室温下为自由流动的溶液,在体温下形成静态凝胶,使其能够作为原位治疗肺癌的药物储存库。对于体内实验,使用异种移植肺癌模型评估PDMP的抗肿瘤疗效。结果表明,PDMP可有效抑制肿瘤生长并延长荷瘤BALB/c裸鼠的生存时间。PDMP治疗组的生存时间(53天)显著高于其他组(游离DDP+PTX组为40天,空白PECE组为26天,生理盐水组为25天,p<0.05)。免疫组织化学分析显示,与对照组相比,PDMP组肿瘤的微血管较少且增殖活性较低。因此,PDMP通过微创注射方法原位治疗肺癌可能具有巨大潜力。