Squalene-based nanoparticles in the treatment of septic shock and uncontrolled inflammation

Researchers from the Galien Institute at Paris-Saclay University/CNRS have developed nanoparticles that are effective in the treatment of severe inflammatory processes, which can be found in many pathologies, such as COVID-19. This research was published recently in the journal Science Advances.

Uncontrolled inflammatory processes are a major health concern because they are the origin of many severe or even lethal pathologies. For example, some COVID-19 patients experience a deterioration in their condition after an uncontrolled inflammatory reaction that leads to respiratory failure, sometimes requiring intubation and resuscitation, or even death. Currently, very few treatments are effective in controlling such severe inflammation, and those that do exist have undesirable side-effects.

Studies carried out over the past two decades tend to show that these states of prolonged severe inflammation are caused by a combination of two factors, inflammation combined with oxidative stress, contributing to feed each other and thus establishing a vicious circle capable of perpetuating and propagating the inflammatory response.

The introduction of nanotechnologies in pharmacology has revolutionised the administration of drugs, in particular thanks to the principle of vectorisation. Drug delivery is based on the principle of ‘targeting’, which consists of encapsulating the drug in a nanovector (most often a liposome, nanoparticle or micelle), so that it delivers its active principle only after reaching the target tissue and penetrates the diseased cell.

Generally between 20 and 300 nanometres, the small size of these therapeutic devices allows them to protect the active ingredient, cross certain biological barriers and deliver the drug more effectively into the body. The objective of targeting is therefore to improve the effectiveness of the treatments while obtaining better control of their therapeutic index, which makes it possible to reduce their toxicity and limit their side-effects.

In collaboration with others, researchers at the Galien Institute have combined different active ingredients within the same nanoparticle by conjugating squalene, a natural lipid, with adenosine, an immunomodulator, and then combining it with alpha-tocopherol, a natural antioxidant.

The researchers’ in vivo study in an animal model of septic shock demonstrated that by exploiting dysfunctions of the endothelial barrier at the sites of acute inflammation, these multidrug nanoparticles could deliver therapeutic agents in a targeted manner, abrogated the hyper-inflammatory response and resulted in significantly improved chances of survival.