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

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.

Graphical abstractThe antitumor effects of rIL-2 loaded microspheres in BALB/c mice bearing colon carcinoma. All mice were euthanized on day 22, and tumors were stripped, weighed and photographed. (A) Representative photographs of tumors. (B) Representative photographs of BALB/c mice bearing tumors. (C) Tumor volumes in the different groups (blank microspheres, rIL-2 solution, rIL-2 loaded microsphere) as a function of day after treatment. (D) Tumor weights of day 22 after mice were euthanized, and the data were expressed as mean ± SD (n = 4).Figure optionsDownload full-size imageDownload high-quality image (76 K)Download as PowerPoint slide