Inhibition of IL-1β release by Necrosulfonamide-loaded porous nanoparticles

Inflammation is an essential physiological response of the body to defend itself against pathogens such as bacteria. It can however become problematic when it turns into a chronic condition, such as in cancers, autoimmune diseases or certain viral infections. Many treatments already exist, but their action is often not very targeted, high doses are required and deleterious side effects are frequent. Macrophages, large immune cells whose natural function is to absorbs pathogens and trigger inflammation to destroy them, are often involved in inflammatory diseases. When overactivated, they trigger an excessive inflammatory response that turns against the body instead of protecting it.

Necrosulfonamide is a new molecule that inhibits the release of several important pro-inflammatory mediators, therefore constituting a promising advance to reduce certain types of inflammation. However, being extremely hydrophobic in nature, it travels poorly in the bloodstream and could target many cell types, triggering potentially toxic effects. The use of nanoparticles to encapsulate a drug to protect it and the body until it reaches its point of action is being increasingly studied. However, this requires identifying the right nanoparticle for each drug according to a series of precise parameters.

A team from the University of Geneva and the Ludwig Maximilians Universität München has succeeded in developing a fully biodegradable nanoparticle capable of delivering a new anti-inflammatory drug directly into macrophages—the cells where uncontrolled inflammatory reactions are triggered ensuring its effectiveness. In addition, the scientists used an in vitro screening methodology, thus limiting the need for animal testing. These results, recently published in the Journal of Controlled Release, open the way to an extremely powerful and targeted anti-inflammatory treatment.

The scientists tested different porous nanoparticles, with the main criteria being a reduction in toxicity and in the required dosage, as well as the ability to release the drug only once the nanoparticle has reached the interior of the macrophages. Three very different nanoparticles featuring high porosity were examined: a cyclodextrin-based nanoparticle, a substance commonly used in cosmetics or industrial food, a porous magnesium phosphate nanoparticle, and finally a porous silica nanoparticle.

The developed porous silica nanoparticle was fully biodegradable, of the right size to be swallowed by macrophages, and was able to absorb the drug into its numerous pores without releasing it too early. The anti-inflammatory effect was remarkable. Indeed mesoporous silica is increasingly revealing itself as a nanoparticle of choice in the pharmaceutical field, as it is very effective, stable and non-toxic. Nevertheless, each drug requires a tailor-made carrier: the shape, size, composition and destination of the particles must be reassessed each time. The combination of this potent anti-inflammatory drug and these mesoporous silica nanoparticles shows a promising synergism to be further studied by the team. The new study demonstrates the potential of porous nanoparticles for the effective delivery of hydrophobic drugs to macrophages in order to suppress inflammatory responses.