Nanogel-based delivery of mycophenolic acid ameliorates systemic lupus erythematosus in mice

J Clin Invest. 2013 Apr;123(4):1741-9. doi: 10.1172/JCI65907.


The ability to selectively inactivate immune cells with immunosuppressants is a much sought-after modality for the treatment of systemic lupus erythematosus and autoimmunity in general. Here, we designed and tested a novel nanogel drug delivery vehicle for the immunosuppressant mycophenolic acid (MPA). Treatment with MPA-loaded nanogels increased the median survival time (MST) of lupus-prone NZB/W F1 mice by 3 months with prophylactic use (MST was 50 weeks versus 38 weeks without treatment), and by 2 months when administered after the development of severe renal damage (MST after proteinuria onset was 12.5 weeks versus 4 weeks without treatment). Equivalent and greater doses of MPA administered in buffer were not efficacious. Nanogels had enhanced biodistribution to organs and association with immune cells. CD4-targeted nanogels yielded similar therapeutic results compared with nontargeted formulations, with protection from glomerulonephritis and decreases in IFN-γ-positive CD4 T cells. DCs that internalized nanogels helped mediate immunosuppression, as they had reduced production of inflammatory cytokines such as IFN-γ and IL-12. Our results demonstrate efficacy of nanogel-based lupus therapy and implicate a mechanism by which immunosuppression is enhanced, in part, by the targeting of antigen-presenting cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blood Urea Nitrogen
  • Cells, Cultured
  • Cyclodextrins / chemistry
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / physiopathology
  • Lactic Acid / chemistry
  • Liposomes
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / physiopathology
  • Mice
  • Mice, Inbred BALB C
  • Mycophenolic Acid / administration & dosage*
  • Mycophenolic Acid / pharmacokinetics
  • Nanocapsules
  • Nanoconjugates* / chemistry
  • Nanoconjugates* / ultrastructure
  • Polyesters
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry
  • Proteinuria / immunology
  • Proteinuria / physiopathology
  • Proteinuria / prevention & control
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Tissue Distribution


  • Cyclodextrins
  • Liposomes
  • Nanocapsules
  • Nanoconjugates
  • Polyesters
  • Polymers
  • Lactic Acid
  • Polyethylene Glycols
  • poly(lactide)
  • Mycophenolic Acid