Potentiels des poly-hydroxyalcanoates (PHAs) bactériens pour l'encapsulation de molécules à visée thérapeutique

Abstract : Poly(HydroxyAlkanoates) (PHA) are natural polymers, biodegradable and biocompatible, synthesized by many organisms, especially prokaryotes. There are over 150 kinds of these polyesters, accumulated in a wide variety of bacteria as carbon and energy storage material. PHA granules are deposited intracellularly when microorganisms are cultivated in the presence of an excess of carbon source (glucids, fatty acids...) together with a nitrogenous nutrient deficiency. Due to their biodegradability and biocompatibility, PHA can be used as biomaterials in medical or pharmaceutical fields, and numerous therapeutic micro/nanovectors have already been developed over the past two decades.The present PhD research project highlighted molecular screening methods by PCR for the PHA producing Bacteria selection, isolated during Ifremer cruises from hydrothermal vents in Atlantic and Pacific oceans.According to standardized and optimized fermentation protocols, poly(3-hydroxybutyrate-4-hydroxybutyrate) P(3HB4HB) polymers of biomedical interest were produced, then taxonomic and phylogenetic studies were performed to explore microbial biodiversity associated with deep-sea environments. Next, PHA were modified by ‘click chemistry’ to obtain hydrosoluble copolymers, suitable for coating high porous Metal-Organic Frameworks (MOF) therapeutic nanoparticles. Physico-chemical characterization was performed using different techniques, and more particularly by SEM and STEM-EDX. MOF-PHA hybrid porous systems were then evaluated for their biocompatibility against immune cells (macrophages), by cytotoxicity and cellular proliferation tests. This study highlights potentials of these new generations of nanovectors, synthesized to increase the therapeutic benefit while minimizing side effects on the human body.
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Submitted on : Wednesday, May 29, 2019 - 5:49:07 PM
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Caroline Jain-Beuguel. Potentiels des poly-hydroxyalcanoates (PHAs) bactériens pour l'encapsulation de molécules à visée thérapeutique. Microbiologie et Parasitologie. Université de Bretagne occidentale - Brest, 2018. Français. ⟨NNT : 2018BRES0095⟩. ⟨tel-02144051⟩



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