Journal article

Targeted delivery of mycophenolic acid to the mesenteric lymph node using a triglyceride mimetic prodrug approach enhances gut-specific immunomodulation in mice

Ruby Kochappan, Enyuan Cao, Sifei Han, Luojuan Hu, Tim Quach, Danielle Senyschyn, Vilena Ivanova Ferreira, Given Lee, Nathania Leong, Garima Sharma, Shea Fern Lim, Cameron J Nowell, Ziqi Chen, Ulrich H von Andrian, Daniel Bonner, Justine D Mintern, Jamie S Simpson, Natalie L Trevaskis, Christopher JH Porter



The mesenteric lymph nodes (MLN) are a key site for the generation of adaptive immune responses to gut-derived antigenic material and immune cells within the MLN contribute to the pathophysiology of a range of conditions including inflammatory and autoimmune diseases, viral infections, graft versus host disease and cancer. Targeting immunomodulating drugs to the MLN may thus be beneficial in a range of conditions. This paper investigates the potential benefit of targeting a model immunosuppressant drug, mycophenolic acid (MPA), to T cells in the MLN, using a triglyceride (TG) mimetic prodrug approach. We confirmed that administration of MPA in the TG prodrug form (MPA-TG), increased lymphati..

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Awarded by Australian Research Council

Funding Acknowledgements

We are grateful to; to Dr. Yanwei Wu and Prof Jianping Zuo at Shanghai Institute of Materia Medica, Chinese Academy of Sciences for their contributions to preliminary screening and discussion that informed model selection in the current studies and to Ms. Sandy Fung and Mr. Timothy Brown and the Imaging, FACS and Analysis Core, Monash Institute of Pharmaceutical Sciences for assistance with flow cytometry and imaging. We also acknowledge assistance from the Harvard Medical School Centre for Immune Imaging and the HMSTrust analytical laboratory at Monash University. Funding support was received from the Australian Research Council (CE140100036)