Développement de nouveaux systèmes nanoparticulaires pour l'administration de bio-médicaments par voie orale

Abstract : Biologics are administrated by parenteral route due to their degradation in the gastrointestinal tract. This administration mode leads to lowadherence, showed by the low adherence for chronic diseases treatment. In order to increase adherence by reducing pain and adverse effects associated with treatment we developed a double encapsulation system to protect and increase biologic absorption for a future oral administration. Our system consists in encapsulated biologics inside PLGA nanoparticles (NPs), themselves encapsulated inside a gastroresistant vehicle. The aim of this work was to improve the system efficiency with insulin by NPs charges modification and intestinal release reduction and to transfer the technology to another molecule: the heparin. Negative charges improved the intestinal nanoparticle crossing as shown by the insulinopenic rat model with a decrease of glycaemia. To stabilize the NPs system in intestinal medium, a hyaluronic acid coating was tested and validated in vitro. When transferred to another biologics, we showed similar NPs chacacteristics with heparin than with insulin, revealing the transposition of our technic.
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Elodie Czuba. Développement de nouveaux systèmes nanoparticulaires pour l'administration de bio-médicaments par voie orale. Pharmacie galénique. Université de Strasbourg, 2018. Français. ⟨NNT : 2018STRAJ072⟩. ⟨tel-02285538⟩

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