Apport des nanotechnologies dans le domaine des peptides et des protéines : Application à l'absorption par voie orale et à la furtivité

Abstract : Nanoparticles are innovative dosage forms in drug delivery. They can act as prolonged release dosage forms but they also have the potentiality to target specific physiological compartments after in vivo administration. This thesis is based on the preparation of nanoparticles according to a double emulsion process. The nanoparticles are formed of two biocompatible polymers: poly-e-caprolactone and a polyacrylic and polycationic polymer (Eudragit® RS). The first part describes the development of insulin-loaded nanoparticles able to release insulin both in vitro and in vivo. It has been demonstrated that such nanoparticles incorporated high amounts of insulin and were able to display a hypoglycemic activity after oral administration. It is well known that the major drawback of diabetes treatment remains the injectable administration route for insulin. The ability to administer insulin orally would be a tremendous progress in the field of diabetes. Our prepared nanoparticles have demonstrated their ability to reduce blood glucose in diabetic rats after oral administration. It is believed that the positively charged insulin-loaded nanoparticles may interact with the negatively charged mucus and create a high local gradient concentration which would favor the intestine permeation. The second part of the thesis was devoted to the development of stealth nanoparticles able to avoid the recognition by the mononuclear phagocytosis system after intravenous administration. The objective was to create a new system based on the formation of electrostatic interactions between heparin, a polyanionic glycosaminoglycane, and Eudragit® RS, polycationic polymer. The stealth potential has been demonstrated by increasing the in vivo plasma half-life of two drugs namely propranolol hydrochloride and insulin.
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Marie Socha. Apport des nanotechnologies dans le domaine des peptides et des protéines : Application à l'absorption par voie orale et à la furtivité. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2008. Français. ⟨NNT : 2008NAN10118⟩. ⟨tel-01777272⟩

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