Medical Devices Prove Effective as Targeted Drug Carriers

Nanoparticles that have been found to be effective in the treatment of severe inflammatory processes have been developed by researchers from the Galien Institute at Paris-Saclay University/ CNRS.

 Uncontrolled severe inflammatory processes, which can be found in many pathologies such as Covid-19 infections in patients, can lead to respiratory failure, sometimes requiring intubation and resuscitation or even resulting in death. Currently, very few treatments are effective in controlling such severe inflammation and those that do exist have undesirable side effects.

Nanotechnologies, such as those developed at the Galien Institute, can now be used to target specific areas in the body using drugs encapsulated in a nanovector (most often a liposome, nanoparticle or micelle). 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 the Plateforme d'Histologie Immunopathologie de Clamart (PHIC), also part of Paris-Saclay University, and the Institut Paris Saclay Innovation thérapeutique (Univ. Paris-Saclay, Inserm, CNRS), 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(1) in an animal model of septic shock demonstrated that by exploiting dysfunctions of the endothelial barrier at the sites of acute inflammation, these multi-drug nanoparticles could deliver therapeutic agents in a targeted manner, abrogated the hyper-inflammatory response and resulted in significantly improved chances of survival in treated animals.

These promising results pave the way for other clinical studies that could lead to the development of effective new drugs to combat severe and uncontrolled inflammation and open up new avenues to mitigate paradoxical inflammatory reactions such as those associated with Covid-19 infections.

Reference

(1) Published in Science Advances, 27 April, 2020.

Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled  inflammation Authors Flavio Dormont1 , Romain Brusini1 , Catherine Cailleau1 , Franceline Reynaud1,2, Arnaud Peramo1 , Amandine Gendron1 , Julie Mougin1 , Françoise Gaudin3,4, Mariana Varna1 , Patrick Couvreur1

Affiliations

 1  Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.

 2  School of Pharmacy, Federal University of Rio de Janeiro, 21944-59 Rio de Janeiro, 16 Brazil.

3 Plateforme d’Histologie Immunopathologie de Clamart (PHIC) Université Paris-Saclay, Inserm, CNRS, Institut Paris Saclay d'Innovation thérapeutique, 92296, Châtenay- Malabry, France.

4  Université Paris-Saclay, Inserm, Inflammation, Microbiome and Immunosurveillance, 92140, Clamart, France