397353 PEGDA Cross-Linked Pnipam Microgel Particles for Protein Delivery to Macrophages

Monday, November 17, 2014
Galleria Exhibit Hall (Hilton Atlanta)
Christopher Isely1, Kiva Forsmark1 and Kaitlin Bratlie2, (1)Chemical and Biological Engineering, Iowa State University, Ames, IA, (2)Chemical and Biological Engineering, Materials Science and Engineering, Iowa State University, Ames, IA

Macrophages phenotypically exist on a spectrum, with M1 classically activated macrophages and M2 alternatively activated macrophages being the ends of this spectrum. Tumor associated macrophages (TAMs) are M2-like and promote tumors. Interleukin-12 (IL-12) has been shown to reprogram M2 macrophages to M1 macrophages, which are tumor regressive. Local delivery of this protein to the tumor microenvironment will lead to repolarization of TAMs to tumor-toxic M1 macrophages. Poly(N-isopropylacrylamide)-co-acrylic acid-co-poly(ethyleneglycol) diacrylate (pNIPAm-co-AAc-co-PEGDA) mcrogel particles were synthesized to be used as a drug delivery vehicle for IL-12. LPS stimulated macrophages are used to model M1 macrophages in vitro. IL-4 stimulate macrophages are used to model M2-like macrophages in vitro. The cytotoxicity, degradative properties, macrophage cytokine secretion profiles, particle internalization and FITC release was studied. Viability of polarized macrophages in the presence of these particles was found to be above 70%. These particles showed evidence of degradation after 2 days. Internalization of these particles by RAW 264.7 macrophages has been shown. Results from this work will be applied to the design of a drug delivery vehicle that will be used to increase the efficacy of drug-based tumor cytotoxicity.

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