Functional Interleukin-4 releasing microparticles impact THP-1 differentiated macrophage phenotype

Abstract

Macrophage cell therapies offer potential treatment in inflammatory diseases due to their ability to mobilize and stimulate their environment. However, successful treatment requires a pro-regenerative macrophage phenotype to be retained in vivo. Polymeric microparticles may provide a potential route to direct and sustain macrophage phenotype. Interleukin-4 (IL-4) is the most commonly used cytokine for in vitro modulation towards M2a macrophage phenotype. We designed IL-4 encapsulated microparticles to investigate the impact of drug release kinetics and developed a robust THP-1 in vitro assay to assess functional IL-4 release upon macrophage phenotype. Microparticles, fabricated from PLGA and a PLGA-PEG-PLGA triblock copolymer were encapsulated with IL-4 and human serum albumin (HSA) for sustained release. IL-4 release kinetics fit with the first-order release kinetics model, indicating concentration dependent release. IL-4/HSA encapsulated microparticles modulated human peripheral blood monocyte cell (THP-1) differentiated macrophages towards pro immunoregulatory subgroups. This strategy provides a novel approach in drug carrier development for in vitro assessments of macrophage phenotype to inform development of targeted therapies for inflammation and immune modulation.