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Etude multi-échelle d'hydrogels stimulables d'acide hyaluronique pour la délivrance d'insuline

Abstract : This work aims to evaluate potential glucose sensitive hydrogels formulations as new medicine to treat diabetes. The gels have to be biocompatible and bioresorbable in vivo. To do so, we choose matrices of polysaccharide enzymatically degradable made of hyaluronic acid (HA). Crosslinking of the HA is done by radical polymerization reactions using methacrylates or thiol-ene chemistry. Glucose sensitivity is introduced thanks to phenylboronic acid moieties (PBA). PBAs are known for their ability to create reversible bonding with diols from saccharides. Two kind of gels are studied: simples ones where PBAs are grafted on the matrix, and doubly crosslinked ones where maltose groups grafted on HA form a second network, which can dissociate upon glucose addition. We investigated the ability of these materials to encapsulate and deliver insulin with the good pharmacokinetics. As kinetics depend on gel sizes, we worked at different scales, from macroscopic to nanometric scale, which allows release in the blood stream. Nano and microgels are prepared thanks to water-in-oil emulsions using respectively high pressure homogeneiser or microfluidic devices. Droplets formed are used as nano/microreactors where crosslinking of modified HA is photoinitiated. Micrometric scale is chosen to study interactions between insulin and model proteins with gel matrices, using confocal microscopy. This technique allows to study composition and structural effects. Encapsulation and release of proteins are studied as well as swelling variations. Then, encapsulation and release of insulin upon addition of monosaccharide is investigated quantitatively for macrogels, after formulation optimization.
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https://tel.archives-ouvertes.fr/tel-01956588
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Submitted on : Sunday, December 16, 2018 - 1:03:20 AM
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  • HAL Id : tel-01956588, version 1

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Helene Labie. Etude multi-échelle d'hydrogels stimulables d'acide hyaluronique pour la délivrance d'insuline. Autre. Université de Bordeaux, 2017. Français. ⟨NNT : 2017BORD0859⟩. ⟨tel-01956588⟩

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