Mal-PEG-PLGA/PEG-PLGA from PolySciTech Used in Development of immune-modulating treatment for multiple sclerosis

 

Several diseases in the human body are driven by a pathological over-reaction of the human immune system. Examples of this include crohn’s disease, and multiple schlerosis. In the case of multiple sclerosis the immune system attacks the nerve coverings leading to severe, chronic disease. Recently, researchers at Drexel University and University of Pennsylvania used Mal-PEG-PLGA (AI020) and mPEG-PLGA (AK037) from PolySciTech (www.polyscitech.com) division of Akina, Inc. to create antigen decorated nanoparticles to prevent the immune system from attacking the nerve tissue. This research holds promise to provide for development of immune tolerance as a treatment for autoimmune diseases. Read more: Li, Peter Y., Frank Bearoff, Pu Zhu, Zhiyuan Fan, Yucheng Zhu, Mingyue Fan, Laura Cort, Taku Kambayashi, Elizabeth P. Blankenhorn, and Hao Cheng. "PEGylation enables subcutaneously administered nanoparticles to induce antigen-specific immune tolerance." Journal of Controlled Release. https://www.sciencedirect.com/science/article/pii/S0168365921000225

“Abstract: The development of nanomaterials to induce antigen-specific immune tolerance has shown promise for treating autoimmune diseases. While PEGylation has been widely used to reduce host immune responses to nanomaterials, its tolerogenic potential has not been reported. Here, we report for the first time that a subcutaneous injection of PEGylated poly(lactide-co-glycolide) (PLGA) nanoparticles containing auto-antigen peptide MOG35–55 without any tolerogenic drugs is sufficient to dramatically ameliorate symptoms after disease onset in an antigen-specific manner in a mouse model of multiple sclerosis. Neither free MOG35–55 nor particles without PEG exhibit this efficacy. Interestingly, mechanistic studies indicate that PEGylation of nanoparticles does not reduce dendritic cell activation through direct nanoparticle-cell interactions. Instead, PEGylated nanoparticles induce lower complement activation, neutrophil recruitment, and co-stimulatory molecule expression on dendritic cells around the injection sites than non-PEGylated PLGA nanoparticles, creating a more tolerogenic microenvironment in vivo. We further demonstrate that the locally recruited dendritic cells traffic to lymphoid organs to induce T cell tolerance. These results highlight the critical role of surface properties of nanomaterials in inducing immune tolerance via subcutaneous administration. Keywords: Immunotherapy Local immune modulation Immune cell recruitment Anergy Experimental autoimmune encephalomyelitis Biomaterials”