Department of Neurology, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai 200092, China.
Int J Pharm. 2013 Jun 25;450(1-2):235-40. doi: 10.1016/j.ijpharm.2013.04.051. Epub 2013 Apr 25.
In this study, we formulated a rIL-2 loaded sustained-release dextran/PLGA-PLA core/shell microsphere, mimicking the paracrine mechanisms of cytokine action, to investigate its local antitumor efficacy. The presented microspheres were formed in two steps: rIL-2 was firstly loaded into dextran particles to keep its bioactivity by a unique method of stabilizing aqueous-aqueous "emulsion"; subsequently, the particles were encapsulated into poly(dl-lactide-co-glycolide)/polylactic acid (PLGA/PLA). A stable sustained release behavior in vitro was achieved for a period of about 25 days. In the subcutaneous colon carcinoma BALB/c mice models, a single dose of microspheres was introtumorally administrated and compared with multiple doses of rIL-2 solution to investigate the long acting effect of microspheres on tumor. The animal experiments showed the local efficacy at tumor site mediated by rIL-2 from a single dose of microspheres was better than that of multiple rIL-2 solution injections. Based on the experimental results, we conclude that rlL-2 loaded sustained-release dextran/PLGA-PLA core/shell microspheres represent a promising approach for local cancer treatment in animals.
在这项研究中,我们制备了负载 rIL-2 的葡聚糖/PLGA-PLA 核/壳微球,模拟细胞因子作用的旁分泌机制,以研究其局部抗肿瘤疗效。所提出的微球分两步形成:首先通过稳定水-水“乳液”的独特方法将 rIL-2 加载到葡聚糖颗粒中以保持其生物活性;随后,将颗粒包封到聚(丙交酯-共-乙交酯)/聚乳酸(PLGA/PLA)中。体外达到了大约 25 天的稳定缓释行为。在皮下结肠癌 BALB/c 小鼠模型中,瘤内单次给予微球,并与 rIL-2 溶液多次剂量进行比较,以研究微球对肿瘤的长效作用。动物实验表明,rIL-2 从单次微球给药介导的肿瘤部位局部疗效优于多次 rIL-2 溶液注射。基于实验结果,我们得出结论,负载 rIL-2 的缓释葡聚糖/PLGA-PLA 核/壳微球为动物局部癌症治疗提供了一种有前途的方法。