Scientists at Yale University in the US have designed and tested a drug delivery system that shows promise for improved treatment of lupus and other chronic autoimmune diseases, such as multiple sclerosis and Type 1 diabetes.
In systemic lupus erythematosus, the body attacks itself for largely mysterious reasons, leading to serious tissue inflammation and organ damage. Current drug treatments address symptoms only and can require life-long daily use at toxic doses.
In a study published online on 1 March in The Journal of Clinical Investigation, Yale researchers used biodegradable nanoparticles to deliver relatively low drug doses that extended the lives of laboratory animals. In tests on mice, prophylactic use of the drug-laden nanoparticles, called nanogels, increased by three months the median survival time of lupus-prone mice, and by two months mice that already had severe kidney damage, a common consequence of lupus.
‘Three months of a mouse’s life is roughly equivalent to more than eight years of a human life, so this is dramatic,’ said Tarek Fahmy, Associate Professor of Biomedical Engineering at Yale, a principal investigator of the paper. ‘We’ll keep at this, because the potential for human benefit is clear and promising.’
Compared with conventional lupus therapies, the biodegradable nanogels proved better at delivering drugs to cells and better at retaining drugs within the body, allowing for significantly lower doses, the researchers said.
We’ll keep at this, because the potential for human benefit is clear and promising
Results also suggest that drug delivery via nanogels works without depleting all white blood cells, leaving recipients less vulnerable to infection.
‘We’ve found a very promising starting point,’ said Michael Look, a postdoctoral researcher in bioengineering at Yale and the paper’s lead author.
Highly stable, the nanogels are essentially micro-vessels made of organic materials that transport and release drugs. They can circulate for longer in the body than conventional drugs due to their size and ability to pass biological barriers. In addition they can be programmed to target specific cells – in the case of lupus, T cells and antigen-presenting cells. In a similar way to existing lupus treatments, they work by deactivating specific immune cells, suppressing their response and minimising lupus symptoms.
The Yale researchers loaded the nanogels with mycophenolic acid, a form of which is used in lupus patients.
The nanogel system has not yet been tested in humans. But the nanogels are made of FDA-approved materials, which could hasten the process involved in preparing them for human use.
The paper is entitled: ‘Nanogel-based delivery of mycophenolic acid ameliorates systemic lupus erythematosus in mice’. The other authors are Eric Stern, Qin Wang, Leah DiPlacido and Michael Kashgarian.