Local antitumor effects of intratumoral delivery of rlL-2 loaded sustained-release dextran/PLGA-PLA core/shell microspheres

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• 作者：Haiping Zhao^a ; ^c ; ¹ ; Fei Wu^c ; ¹ ; Yunpeng Cai^c ; Yinghui Chen^b ; ^{cyh1973131@163.com} ; Liangming Wei^d ; ^{lmwei@sjtu.edu.cn} ; Zhenguo Liu^a ; ^{zhenguoliu2011@yahoo.com.cn} ; Weien Yuan^c ; ^{yuanweien@126.com}
• 关键词：rlL-2 loaded sustained-release dextran/PLGA&ndash ; PLA core/shell microspheres ; Aqueous&ndash ; aqueous emulsion ; Local cancer treatment
• 刊名：International Journal of Pharmaceutics
• 出版年：2013
• 出版时间：25 June, 2013
• 年：2013
• 卷：450
• 期：1-2
• 页码：235-240
• 全文大小：1333 K

文摘

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.