Thèse Synthèse de Matériaux Biosourcés à Base de Cyclodextrines Appliqués à la Libération Contrôlée de Principes Actifs pour des Applications Pharmaceutiques H/F - 75

Établissement : Université Paris-Saclay GS Chimie
École doctorale : Sciences Chimiques : Molécules, Matériaux, Instrumentation et Biosystèmes
Laboratoire de recherche : Institut Galien Paris-Saclay
Direction de la thèse : Nathalie JARROUX ORCID 0000000335859758
Début de la thèse : 2026-10-01
Date limite de candidature : 2026-03-31T23:59:59

Ce projet vise à développer une nouvelle génération de matériaux biosourcés et biodégradables dont les propriétés structurales (porosité, biodégradabilité, densité de réticulation chimique/physique, taux et nature des modifications chimiques, type de cage moléculaire à base de cyclodextrines) seront finement contrôlées afin de concevoir des supports poreux fonctionnels pour des applications en vectorisation thérapeutique.
La première étape consistera à élaborer et caractériser des films Langmuir-Blodgett et des films imprimés en 3D, permettant d'identifier l'influence des paramètres structuraux sur la morphologie, la stabilité et les propriétés mécaniques et physico chimiques des matériaux. Dans un second temps, ces matrices seront chargées en principes actifs thérapeutiques ou biologiques, selon différentes stratégies (avant ou après structuration), afin d'étudier les cinétiques de libération en lien avec l'architecture moléculaire et la microstructure des supports.
Les matériaux présentant les meilleures performances (contrôle de la libération, stabilité, propriétés mécaniques) et une biocompatibilité démontrée in vitro seront ensuite sélectionnés pour des évaluations in vivo. Ce projet permettra d'établir des relations structure-propriété-fonction essentielles pour la conception de biomatériaux innovants, ouvrant la voie à des systèmes de délivrance thérapeutique plus sûrs, plus durables et entièrement biosourcés.

Biomaterials based on cyclodextrin to active delivery
Cyclodextrin based supramolecular biomaterials have emerged as a highly promising platform thanks to their reversible host-guest interactions, which provide injectability, self healing behavior, and controlled drug release. Current approaches rely either on pseudopolyrotaxanes, where cyclodextrins are threaded onto polymer chains, or on inclusion complexes formed with hydrophobic guest molecules such as adamantane, azobenzene, or ferrocene. These strategies enable the design of dynamic, stimuli responsive, and mechanically tunable materials. Such materials and often hydrogels show remarkable performance in skin wound healing, corneal regeneration, and bone repair, particularly due to their ability to stabilize therapeutic molecules and mimic biologically relevant microenvironments. Remaining challenges include improving mechanical robustness, controlling degradation, and advancing clinical translation, but the outlook is highly favorable, especially with the integration of 3D bioprinting and active molecules delivery systems.

This doctoral research project aims to design biobased materials for the controlled delivery of active molecules in pharmaceutical applications. To achieve the objectives of this project, the work plan will be divided into three parts.:

Objective 1: Synthesis of CyclodextrinBased Materials with Controlled Structural Parameters
Objective 2: Enhancement of Active Molecule Loading and Release Control through Structural Integration
Objective 3: Biological Evaluation and Structure-Activity Relationship Analysis

This doctoral research project aims to design biobased materials for the controlled delivery of active molecules in pharmaceutical applications. To achieve the objectives of this project, the work plan will be divided into three parts.

Objective 1: Synthesis of CyclodextrinBased Materials with Controlled Structural Parameters
- Hypothesis 1: Biobased materials can be synthesized with varying physical and chemical proportions of crosslinkers, degrees of modification, and encapsulation efficiencies.
- Hypothesis 2: These materials can be organized into thin films using a Langmuir balance or processed via 3D printing, enabling the study of their mechanical properties.
- Hypothesis 3: The most promising materials can be produced in sufficient quantities to allow drug complexation and subsequent in vitro biological testing on cells.

Objective 2: Enhancement of Active Molecule Loading and Release Control through Structural Integration
- Hypothesis 4: The intrinsic morphology of the materials is sufficient to influence and regulate the behavior of active molecules.
- Hypothesis 5: Drug release profiles can be further tuned for pharmaceutical applications such as drug delivery and/or cell growth and differentiation.
- Hypothesis 6: The optimal configurations for pharmaceutical applications can be produced at a larger scale to enable ex vivo and in vivo studies.

Objective 3: Biological Evaluation and Structure-Activity Relationship Analysis
- Hypothesis 7: The morphology of the materials can be adjusted to modulate key parameters such as pharmacodynamics and pharmacokinetics.
- Hypothesis 8: The quantity of material can be varied to influence dosage and support personalized medicine approaches.
- Hypothesis 9: Local tolerance and biodegradability will be evaluated as a function of the materials' morphologies.

This structured approach aims to develop a new generation of cyclodextrinbased materials and assemblies, combining precise molecular engineering with advanced strategies for the controlled delivery of active molecules.