The uptake of PLGA micro or nanoparticles by macrophages provokes distinct in vitro inflammatory response

Biodegradable micro/nanoparticles generated from PLGA have recently attracted attention due to their clinically proven biocompatibility, especially for immunization purposes. These polymeric particulate delivery systems are able to present antigens and activate both humoral and cellular responses. Many studies have discussed the ideal size of these particles in contributing to the generation of the different types of immune response. However, these studies do not demonstrate the effect of micro or nanoparticles, without any encapsulated bioactive, on phagocytic cells after the uptake process. In this context, the aim of this study was to analyze the in vitro inflammatory behavior of J774 murine macrophages after particles' uptake, since nano/microparticles per se can differently activate phagocytic cells, using or not appropriate receptors, inducing distinct inflammatory responses. An o/w emulsion solvent extraction-evaporation method was chosen to prepare the particles. We determined their diameters, zeta potential and morphology. Fluorescent particles' uptake by J774 murine “macrophage-like” cells was also analyzed. To evaluate the in vitro inflammatory profile of these cells after micro or nanoparticles' uptake, we conducted NF-κB translocation assay by confocal microscopy and also determined the pro-inflammatory cytokines production provoked by the particles.

Research highlights► PLGA micro/nanoparticles without any encapsulated bioactive compound can differently activate J774 macrophages. ► PLGA microparticles are not able to be phagocytosed by J774 macrophages with the same avidity demonstrated for nanoparticles but instead, they attach to cell membrane and constitute more potent inflammatory stimulus after the uptake process. ► Microparticles are more potent inflammatory stimulus than nanoparticles in activating NF-κB translocation to cell nucleus.