Développement de nanoparticules de polysaccharides naturels, chargées avec une combinaison d’actifs et fonctionnalisées avec du fucoïdane afin de réaliser un traitement ciblé et efficace des accidents vasculaires cérébraux

Cardiovascular diseases pose a global threat to human health, with among them thrombotic diseases such as pulmonary embolism, myocardial infarction and acute ischemic stroke as the major killers. Despite the paramount need for primary prevention, population aging and lifestyle changes still contribute to an increasing burden. While various treatments exist, including the fibrinolytic recombinant tissue plasminogen activator (rtPA), the gold standard for treating acute ischemic strokes, they lack efficacy and often are plagued by severe side effects. The goal of this research was therefore to present a nanomedicine-based approach for improved thrombolysis through delivery of multiple therapeutic agents, addressing the complex nature of thrombi.Consequently, we have developed an innovative synthesis for polysaccharide hydrogel nanoparticles capable of loading rtPA and DNase I, another enzyme, and studied their thrombolytic effect. The former were biocompatible and safe, imbued with a robust synthesis yielding stable colloidal suspensions that were fully characterized. The synthesis notably involved the microemulsion framework to improve the emulsification process. These nanogels also incorporated fucoidan, thus acquiring a targeting capacity of thrombi through the affinity of fucoidan for P-selectin, a marker of activated platelets and endothelium. Hereafter, the successful drug loadings were validated through different assays, culminating in the in vitro successful synergic degradation of thrombi. Hence, we explored the thrombolytic properties with a murine in vivo thrombosis model, which demonstrated an improved thrombolysis with the loading of rtPA in our nanoparticles, at 50% and 10% the recommended dose. Overall, this work emphasized the potential of fully polysaccharidic polymeric nanoparticles for the targeted treatment of thrombotic diseases.