UPR 5301

Claire Desfrancois’ thesis defense on November 6th, 2020

This thesis is entitled "Design, synthesis and characterization of hydrogels with high compressive strength for the sustainable delivery of hydrophobic drugs", and is co-supervised by both Ms. Rachel Auzély-Velty (Professor at the University of Grenoble Alpes and team leader at CERMAV) and Ms. Isabelle Texier-Nogues, Research Engineer at CEA Leti-L2CB.

Abstract :
The local and sustained delivery of a drug of interest requires the use of a conformable support matrix, able to adjust to patient daily movements. This matrix should be biocompatible, resistant, and should show suitable compressive and stretchable properties. New composite materials for the delivery of hydrophobic active pharmaceutical ingredients (API) have been designed from stretchable hydrogels and lipid nanoparticles able to encapsulate high payloads of hydrophobic drugs. The double encapsulation system – API-loaded lipid nanoparticles embedded in a polymer network with stretchable meshes – could achieve finely-tuned control over drug delivery while improving patient compliance. First, water-soluble polyrotaxanes (PR) were synthesised with a controlled number of threaded cyclodextrins thanks to an original method. These PR were further used as cross-linkers in a photo-crosslinked network of poly(ethylene glycol)-methacrylate. This novel polymeric matrix showed increased compressive properties as demonstrated by mechanical tests. In parallel, new formulations of lipid nanoparticles loaded with two API of interest and their drug release profile were studied, for further inclusion in the stretchable hydrogel matrix.

Keywords : polyrotaxanes, hydrogels, lipid nanoparticles, drug delivery, high compressive strength, double encapsulation