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Nouveaux biomatériaux photosensibles pour des applications antimicrobiennes

Abstract : Although photodynamic therapy was discovered over a hundred years ago for its ability to kill microorganisms, it has been developed mainly as an anti-cancer therapeutic treatment. Recently, with the increasing number of infections caused by multidrug-resistant bacteria, photodynamic antimicrobial chemotherapy (PACT) is considered a promising alternative antimicrobial approach. PACT is a non-invasive therapeutic strategy and is fast acting. Furthermore, PACT does not appear to induce the development of resistance mechanisms by bacteria, making it an attractive alternative to, for example, conventional treatments for wound infections. The most commonly used photosensitizers in PACT are porphyrins and their derivatives. However, these compounds suffer from poor water solubility, self-quenching, and lack of selectivity against bacterial cells. In order to overcome some of the problems related to the use of porphyrins as photosensitizers in PACT, we have focused in this work on two strategies for the optimization of this therapy. The first one consists in coupling a porphyrin to two maltodextrin derivatives (maltohexaose or maltotriose) recently used as bacterial targeting agents for medical imaging, to improve the selectivity of the porphyrin towards bacterial cells. Biological evaluation of these conjugates has shown that the combination of porphyrins with maltooligosacharide increases their antibacterial efficacy against Staphylococcus aureus and Staphylococcus epidermidis. The second strategy aims at incorporating porphyrins into xylan-based hydrogels. For this purpose, three routes were explored: in the first approach, the hydrogel was first synthesized by cross-linking xylan before loading it with a cationic porphyrin. In the second, the porphyrins are first attached by covalent bonds to the xylan, then the hydrogels were obtained from these xylans functionalized by a cross-linking agent. In the third method, the hydrogel is obtained directly by a direct cross-linking of the xylan by the porphyrins. All the hydrogels obtained showed a good mechanical integrity and a high swelling rate and a strong photoantibacterial activity towards Gram (+) and Gram (−) bacteria.
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https://tel.archives-ouvertes.fr/tel-03702495
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Submitted on : Thursday, June 23, 2022 - 10:14:11 AM
Last modification on : Friday, June 24, 2022 - 4:07:28 AM

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Abdechakour El Kihel. Nouveaux biomatériaux photosensibles pour des applications antimicrobiennes. Chimie organique. Université de Limoges, 2022. Français. ⟨NNT : 2022LIMO0048⟩. ⟨tel-03702495⟩

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