New anti-inflammatory treatment acts at the heart of cells

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Swiss and German researchers have developed a biodegradable nanoparticle capable of transporting a new anti-inflammatory drug to the heart of cells that trigger inflammatory reactions so that it is more effective and less toxic.

New anti-inflammatory treatment acts at the heart of cells

How to deliver a medicinal substance exactly where it is needed, while limiting the risk of side effects? There is increasing research into the use of nanoparticles to encapsulate a drug to protect it up to its point of action. However, this requires identifying the appropriate nanoparticle for each drug based on a series of precise parameters. A team from the University of Geneva (UNIGE) and the Ludwig-Maximilian University of Munich (LMU) has managed to develop a fully biodegradable nanoparticle capable of delivering a new anti-inflammatory drug directly to macrophages, the cells where uncontrolled inflammatory reactions are triggered. which guarantees its effectiveness. In addition, the scientists used an in vitro detection methodology, which limited the need for animal testing. These results, recently published in the Journal of Controlled Release, open the way to an extremely powerful and specific anti-inflammatory treatment.

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

Necrosulfonamide (NSA) is a new molecule that inhibits the release of several important pro-inflammatory mediators, making it a promising development in reducing certain types of inflammation. However, being extremely hydrophobic in nature, it moves poorly in the bloodstream and could attack many cell types, triggering potentially toxic effects.

“That is why this molecule is not yet available as a drug,” says Gaby Palmer, a professor at the Department of Medicine and the Geneva Center for Inflammation Research at the UNIGE School of Medicine, who co-led the study. “Using a nanoparticle as a transport vessel would circumvent these shortcomings by delivering the drug directly to macrophages to combat inflammatory overactivation where it starts.”

Three nanoparticles under the microscope

The scientists tested different porous nanoparticles, with the main criterion being the reduction of toxicity and the required dose, as well as the ability to release the drug only once the nanoparticle has reached the interior of the macrophages. “We use an in vitro detection technology that we developed a few years ago in human and mouse cells. This saves time and greatly reduces the need to use animal models,” explains Carole Bourquin, Professor at the Faculties of Science (Western Swiss Institute of Pharmaceutical Sciences) and Medicine (Department of Anesthesiology, Pharmacology, Intensive Care and Emergency) at Translational Research Center in Oncohaematology, Geneva Center for Inflammation Research), who co-led this work at UNIGE. “Therefore, only the most promising particles will be tested in mice,

Three very different nanoparticles exhibiting high porosity were examined: a cyclodextrin-based nanoparticle, a substance commonly used in cosmetics or industrial foods, a porous magnesium phosphate nanoparticle, and finally a porous silica nanoparticle. “The former was less successful in cell uptake behavior, while the latter turned out to be counterproductive: it triggered the release of pro-inflammatory mediators, which stimulated the inflammatory reaction instead of fighting it,” says Bart Boersma, first author of this study.

“The porous silica nanoparticle, on the other hand, ticked all the boxes: it was fully biodegradable, the right size to be swallowed by macrophages, and it could absorb the drug into its many pores without releasing it too early. The anti-inflammatory effect was remarkable.” The team then replicated their tests by coating the nanoparticles with an additional layer of lipids, but with no greater benefit than silica nanoparticles alone.

tiny silica sponges

Other silica nanosponges developed by the German-Swiss team had already proven effective in transporting antitumor drugs. “Here they carry a very different drug that suppresses the immune system,” says Carole Bourquin. “Mesoporous silica is revealing itself more and more as a nanoparticle of choice in the pharmaceutical field, since it is very effective, stable and non-toxic. However, 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 powerful anti-inflammatory drug and these mesoporous silica nanoparticles shows a promising synergism that the team will continue to study.

Source: UNIGE

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