Immunological Evaluation In Vitro of Nanoparticulate Impurities Isolated From Pharmaceutical-Grade Sucrose.

Sucrose is a commonly used stabilizing excipient in protein formulations. However, recent studies have indicated the presence of nanoparticulate impurities (NPIs) in the size range of 100-200 nm in pharmaceutical-grade sucrose. Furthermore, isolated NPIs have been shown to induce protein aggregation when added to monoclonal antibody formulations. Moreover, nanoparticles are popular vaccine delivery systems used to increase the immunogenicity of antigens. Therefore, we hypothesized that NPIs may have immunostimulatory properties. In this study, we evaluated the immunomodulatory effects of NPIs in presence and absence of trastuzumab in vitro with monocyte-derived dendritic cells (moDCs). Exposure of trastuzumab, the model IgG used in this study, to NPIs led to an increase in concentration of proteinaceous particles in the sub-micron range. When added to moDCs, the NPIs alone or in presence of trastuzumab did not affect cell viability or cytotoxicity. Moreover, no significant effect on the expression of surface markers, and cytokine and chemokine production was observed. Our findings showed, surprisingly, no evidence of any immunomodulatory activity of NPIs. As this study was limited to a single IgG formulation and to in vitro immunological read-outs, further work is required to fully understand the immunogenic potential of NPIs.