Amélioration de la biodisponibilité de protéines de la coagulation par formation de conjugués covalents solubles et de nanoparticules : application à la protéine C

Abstract : A lot of biologically active molecules such as coagulation proteins i.e. factor VIII and protein C have a short half-life in blood. Their half-life i.e. their biodisponibility could be increased by means of either the formation of soluble covalent conjugates with a macromolecule or their encapsulation within stealth nanoparticles. Conjugate formation : A study was carried out on model proteins (hemoglobin and albumin) in low-concentration medium with derivatized dextrans but unfortunately, it couId not be applied to coagulation proteins (factor VlII, factor IX and protein C). However, the role of their carboxylate and amino groups could be underlined. Encapsulation : Biodegradable amphiphitic copolymers made of a poly(lactic acid) (PLA) hydrophobic block and of a monomethoxypolyethylene (MPEO) hydrophilic one were synthesized in order to prepare stealth biodegradable nanoparticles of protein C by a double emulsion method. Experimental conditions allowing the preservation of encapsulated protein C characteristics and the optimization of its encapsulation efficiency were determined for non stealth nanoparticles (PLA). The stealth character of blank MPEO-PLA nanoparticles were highlighted in vitro by studying complement consumption and phagocytosis. Afterwards, processing conditions allowing stealth nanoparticles of protein C with a satisfactory active protein C loading, a mean diameter of 200 nm and its progressive release were optimized. Finally, the in vivo behavior of such protein C nanoparticles was studied in guinea pig. Their stealth character and a progressive release of encapsulated protein C were brought to light.
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Theses
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http://docnum.univ-lorraine.fr/prive/SCD_T_1998_0347_ZAMBAUX.pdf
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https://hal.univ-lorraine.fr/tel-01747474
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Submitted on : Thursday, March 29, 2018 - 11:01:00 AM
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Marie-France Zambaux. Amélioration de la biodisponibilité de protéines de la coagulation par formation de conjugués covalents solubles et de nanoparticules : application à la protéine C. Sciences agricoles. Université Henri Poincaré - Nancy 1, 1998. Français. ⟨NNT : 1998NAN11011⟩. ⟨tel-01747474⟩

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