Innovative multidrug nanomedicines for the treatment of myocardial ischemia/ reperfusion injuries

Joint PhD thesis at UNamur and Université Paris-Saclay

Promoters

Prof. Jean-Michel DOGNE, UNamur, NARILIS, Department of Pharmacy

Prof. Mariana VARNA-PANNEREC, Université Paris-Saclay, Institut Galien Paris-Saclay

Jury

• Prof. Jean-Michel Dogné, Université Namur (promoter)
• Prof. Mariana Varna-Pannerec, Université Paris-Saclay (promoter)
• Prof. Hervé Hillaireau, Université Paris-Saclay (president)
• Prof. Karine Andrieux, Université Paris Cité
  
• Prof. Prisca Boisguerin, Université de Montpellier
  
• Prof. Bernard Masereel, Université de Namur

Summary

Myocardial ischemia/ reperfusion is a complex pathological condition involving various signaling mechanisms. Due to their interactions, available treatments for reperfusion injuries often prove insufficient. It is crucial to explore approaches that integrate multiple agents targeting different biological pathways. While nanomedicine offers opportunities to protect active ingredients and optimize therapeutic targeting, it faces challenges like low drug incorporation rates. The squalenoylation method holds potential to address these issues. We first studied squalene-based NPs containing cyclosporine A (SqCsA) in vitro, assessing their toxicity and cardioprotective capacity. We then tested squalene-adenosine formulations (SQAd) in an in vivo mouse model, observing beneficial effects on cardiac function, though statistical significance was not reached. Subsequently, we developed SQAd/Vit E nanoparticles and tested them in an optimized rat model of myocardial ischemia-reperfusion, applying comprehensive analysis methods and captured detailed cardioprotective effects. Finally, we investigated protein corona formation on these nanoparticles to shed light on their in vivo behavior in biological fluids. These findings highlight the potential of novel nanomedical formulations in treating cardiac I/R injuries.