Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
What are nanogels?
Nanogels are synthetic particles that can be used for drug delivery. They are approximately 100 nm to 200 nm in diameter, and are made from safe, biocompatible materials: a gel-like interior and a lipid exterior.
We designed these particles so that they could be used to deliver therapeutic compounds in the body.
Please can you give a brief overview of lupus?
Lupus is an autoimmune disease, in which the immune system mistakenly attacks the organs and tissues of the body.
Symptoms can vary widely between patients, and may include abnormal changes in the blood cells, arthritis, skin rashes, photosensitivity, vasculitis, kidney failure, and neurological disorders.
What treatments are currently available for lupus?
Treatment is based on life-long administration of immunosuppressant drugs that “turn-off” overactive immune cells and inflammation.
The most commonly used drugs are mycophenolate mofetil, cyclophosphamide, and azathioprine, all of which inhibit immune cell proliferation.
Corticosteroids may also be administered to treat inflammation. More recently, a biologic called “Benlysta (belimumab)” has been approved by the U.S. Food and Drug Administration (FDA) in 2011 for lupus treatment; this compound works by inhibiting the growth of a specific type of immune cell know as a “B cell.”
What are the main limitations of current lupus treatments?
Currently used treatments are not effective in all patients and can be toxic. Also, because lupus is a chronic disease with no current cure, treatment regimens are life-long and may need to be constant (daily) in severe cases; this can lead to high non-adherence rates among patients.
Despite these problems, lupus treatments have stayed mostly the same for the past 50 years in the U.S.A.
Where did the idea of using nanogels to attack lupus originate?
We’ve had a long-standing interest in developing nanoparticles for immunotherapeutics, and exploring how nanotechnology can be used to tune the immune system to better treat or prevent diseases.
The idea of treating lupus with nanoparticles arose through discussions with our collaborator, Joe Craft, who is Chief of Rheumatology and Professor of Immunobiology, as well as Director of Investigative Medicine, at Yale University.
One of Joe’s research specialties is lupus autoimmunity, and he presented the challenges with current treatments for lupus and the need for new therapeutic approaches.
What potential therapeutic benefits do nanogels offer over traditional treatments?
We believe that nanogels improve the delivery of active therapeutic compounds to where they are needed in the body, which is a classic theme that motivates much of the development of controlled drug release technologies.
With enhanced delivery of drug to the immune cells that cause lupus, there can be greater efficacy in treatment as well as less frequent dosing requirements.
What did your research on nanogels involve?
The nanogels were loaded with mycophenolic acid, an immunosuppressant that is the active form of the clinically-used drug, mycophenolate mofetil.
We used these nanogels to treat mice that had a genetic predisposition for lupus, and tested whether the particles were efficacious and safe, and if there was any benefit to drug encapsulation within particle.
We also characterized how these nanoparticles interacted with immune cells to achieve immunosuppression.
What did your research find?
We found that nanogels provided much longer survival benefits than a drug regimen without particles.
The particles provided protection from fatal kidney damage, which is associated with lupus, and also attenuated the inflammatory activity of immune cells such as CD4 T cells and dendritic cells.
Also, no hematological, liver, or renal toxicities were observed with nanogels.
Are there plans to test the nanogel system in humans?
We’d like to see how well these nanogels could treat human disease. Before we can do that, we’ll need to verify the safety of these particles in humans with appropriate clinical studies.
Do you think nanogels could be used to treat other autoimmune diseases?
Yes, it’s our hope that these particles could be more broadly used to treat other autoimmune diseases and provide immunosuppression in other clinical contexts, such as allergies or preventing organ transplant rejection.
How was this research funded?
This research was primarily funded by the Lupus Research Institute, an organization based in New York City that is dedicated to novel research in lupus.
We also received support from the Wallace H. Coulter Foundation for development of translational therapeutics for lupus.
Do you have plans for further research into nanogels and lupus?
We are continuing development of these nanotherapies. Among the research avenues we are exploring, we are evaluating how these nanogels can be further optimized for lupus and if other autoimmune diseases could be treated in a similar fashion.
Where can readers find more information?
This work is published in The Journal of Clinical Investigation (first online March 1, 2013), with the article title, “Nanogel-based delivery of mycophenolic acid ameliorates systemic lupus erythematosus in mice.” (doi:10.1172/JCI65907) It is available at the journal website: http://www.jci.org/articles/view/65907
About Dr Look and Dr Fahmy
Michael Look is currently a postdoctoral associate at Yale University, where he received his Ph.D. in Biomedical Engineering and was a fellow of the U.S. National Science Foundation Graduate Research Program and Department of Defense National Defense Science and Engineering Graduate Program.
Tarek Fahmy is an associate professor of Biomedical Engineering at Yale University, with joint appointments in Chemical and Environmental Engineering and Immunobiology. Dr. Fahmy’s research interests lie in the development and application of biomaterials for immunotherapeutics and diagnostics.