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

Journal of Pharmaceutical Sciences
Adam GrabarekWim Jiskoot

Abstract

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 imm...Continue Reading

References

Jul 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Serge N Timasheff
Apr 3, 2008·Journal of Immunotoxicology·M Novak, V Vetvicka
Jul 15, 2009·Immunological Reviews·Helen S GoodridgeDavid M Underhill
Jul 15, 2011·Clinical and Vaccine Immunology : CVI·Eva SonckEric Cox
May 16, 2012·The Journal of Biological Chemistry·Marisa K JoubertVibha Jawa
Mar 28, 2013·Frontiers in Cellular and Infection Microbiology·Anthony E GregoryDiane Williamson
Jun 9, 2014·Trends in Biotechnology·Christopher J Roberts
Jul 15, 2015·Chemical Reviews·Darrell J IrvineTalar Tokatlian
Feb 13, 2016·Journal of Pharmaceutical Sciences·Ehab M MoussaElizabeth M Topp
Apr 6, 2016·Journal of Pharmaceutical Sciences·Wim JiskootLinda O Narhi
May 26, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Naomi BenneBram Slütter
Nov 5, 2016·International Journal of Biological Macromolecules·Mi WangFeiqun Xue
Oct 21, 2016·Cancer Immunology, Immunotherapy : CII·Claire BartonJames F Spicer
Oct 8, 2016·Immunology and Cell Biology·Yann GallaisIsabelle Turbica
Sep 24, 2019·Scandinavian Journal of Immunology·Vaclav VetvickaPetr Sima
Sep 30, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Myriam NabhanUNKNOWN ABIRISK Consortium

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