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Development of nanomedicines for inflammation disorders : evaluation of pharmacological efficacy on preclinical models

Abstract : Advances in drug delivery have led to the development of many tools that help tailor the drug delivery strategy. In particular, “nanomedicines” have made it possible to obtain numerous innovations in oncology and diagnostic technology. By improving drug targeting and protecting the pharmaceutical agent from early metabolism, nanomedicines improve the therapeutic index of certain molecules, resulting in improved patient prognosis. However, with these promises come notable limitations, such as the low drug loading rate of certain nanoformulations, complicated industrial development or poor release control. Squalene-based nanoparticles have been developed to meet these limitations. Another advantage of squalene-based nanoparticles is that they make it possible to encapsulate several therapeutic agents within the same system, thus allowing multi-drug treatments.This is an important tool in the context of an excessive inflammatory response, where many factors often converge to advance the disease. Therefore, one of the objectives of this thesis was to develop and test on preclinical models of inflammation, squalene-based nanoparticles encapsulating two therapeutic agents: adenosine, as an endogenous mediator of inflammatory responses and an antioxidant as an inhibitor of oxidative stress. Our hypothesis is that a multi-drug therapy could be advantageous to counter the many pathogenic processes which reinforce each other during inflammatory responses, but also that a formulation in the form of nanoparticles could provide interesting targeting properties. During the work of this thesis, we also have the feasibility of industrial translation of the synthesis of squalene-based bioconjugates.
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Submitted on : Wednesday, September 2, 2020 - 1:12:03 AM
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  • HAL Id : tel-02927786, version 1



Flavio Dormont. Development of nanomedicines for inflammation disorders : evaluation of pharmacological efficacy on preclinical models. Galenic pharmacology. Université Paris Saclay (COmUE), 2019. English. ⟨NNT : 2019SACLS451⟩. ⟨tel-02927786⟩



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