Lupus is an autoimmune disorder in which the immune system becomes dysregulated, attacking the body's own cells and tissues and causing inflammation and subsequent damage. Systemic lupus erythematosus (SLE) is the most common and serious form of lupus. There is no cure; treatments instead focus on suppressing the immune response in order to minimize organ damage. Many currently available drugs must be taken continually, and some are quite toxic, leading to a high rate of treatment noncompliance. Immunobiologists continue to search for strategies that can target immunosuppressant drugs to specific immune cells, lowering the dose of medication that is effective.

Scientists at Yale University (New Haven, CT) now report successful treatment of a mouse model of SLE using nanogel technology to deliver relatively low but effective doses of the immunosuppressant mycophenolic acid (MPA), a form of which is already used to treat SLE in humans. MPA-loaded nanogels extended mean survival time by 3 months when administered before the onset of disease and by 2 months when administered to mice that had already developed renal failure (J. Clin. Invest. published online 1 March 2013; doi:10.1172/JCI65907). “Three months of a mouse's life is roughly equivalent to more than eight years of a human life, so this is dramatic,” Tarek Fahmy, the lead researcher, told Yale News. “The potential for human benefit is clear and promising.”

Mice treated with MPA-loaded nanogels showed no signs of hematological or organ toxicity, and their white blood cells were not completely depleted, suggesting that nanogel delivery might preserve immune function and reduce the vulnerability to infection that commonly occurs with immunosuppressant therapy.

The nanogel has a biodegradable gel core surrounded by a lipid bilayer, enabling it to encapsulate both hydrophilic and hydrophobic molecules and to stabilize them for delivery. Delivery via nanogel improved distribution of MPA to organs and retention of the drug within the body. Although the nanogels have not yet been tested in human SLE, the nanogel components are approved by the FDA, and similar systems have been tested for delivery of cancer-fighting drugs.

Fahmy says the study is “the first in-depth and comprehensive application of a promising nanotechnology for directed immunosuppressant delivery in a heterogeneous autoimmune disease with limited therapeutic options.” His team suggests that nanogel delivery could prove to be a useful therapeutic strategy in other autoimmune conditions as well.