New potential nanotechnology-based therapies for the treatment of rheumatoid arthritis

Doctorant : Nataliya STOROZHYLOVA
Équipe : Ingénierie Moléculaire et Glycobiologie
Directeur de thèse : Cyrille GRANDJEAN , Directeur de recherche CNRS
co-directeur de thèse : Maria José Alonso Fernandez, Professeur, Université de Saint-Jacques de Compostelle, Espagne
Financement : Union européenne : Erasmus Mundus
Date de la soutenance : vendredi 18 mai 2018, 13h00
Modalité :
Jury :
  • Président de jury : Jérôme Guicheux, Directeur de Recherche, INSERM, Université de Nantes
  • Rapporteur : Pascal Reboul, Professeur, Université de Lorraine
  • Rapporteur : Carmen Evora, Professeur, Université de La Laguna, Espagne
  • Examinateur : Marco Garcia Fuentes, Assistant Professeur, Université de Saint-Jacques de Compostelle, Espagne
  • Directeur de thèse : Cyrille GRANDJEAN , Directeur de recherche CNRS
  • co-directeur de thèse : Maria José Alonso Fernandez, Professeur, Université de Saint-Jacques de Compostelle, Espagne

This thesis project covers the design, development and in vivo evaluation of a novel self-assembled injectable biodegradable drug delivery system (DDS), composed of in situ hydrogel combined with nanocapsules for lipophilic anti-inflammatory drugs, aiming prolonged intra-articular (IA) residence time and controlled drug release. The moderate initial viscosity allows good syringeability, while rheological properties of the assembled DDS enable resistance to high deformations, displaying the hydrogel suitable for IA application. In this regard, to validate the new delivery system, dexamethasone was used as a model drug. Besides, a novel and potential lead compound for immunotherapeutic anti-rheumatic drug candidate – galectin-3 antagonist was synthesized, characterized and evaluated in this study. The preliminary in vivo results demonstrated remarkable suppression of acute joint inflammation by galectin-3 inhibitor encapsulated within hydrogel and administrated IA at microgram scale doses compared to non-treated control. Overall, the work presented here portrays the DDS with encapsulated synthetic galectin-3 inhibitor as a capable in situ nanotechnology-based platform for arthropathies treatment, intended to contribute to efficient joints therapies.


Publications

2020

Storozhylova, Nataliya; Crecente-Campo, José; Cabaleiro, David; Lugo, Luis; Dussouy, Christophe; õ, Sandra Sim; Monteiro, Madalena; Grandjean, Cyrille; Alonso, María J

An In Situ Hyaluronic Acid-Fibrin Hydrogel Containing Drug-Loaded Nanocapsules for Intra-Articular Treatment of Inflammatory Joint Diseases Article

Regenerative Engineering and Translational Medicine, 6 (2), p. 201–216, 2020, ISSN: 23644141.

Résumé | Liens | BibTeX

2018

Dion, Johann; Storozhylova, Nataliya; Dahbi, S; Lambert, Annie; Téletchéa, Stéphane; Dussouy, Christophe; Grandjean, Cyrille

Design and screening of sugar-derived small molecule inhibitors of galectins. Inproceedings

J. Protein Proteomics, 2018.

BibTeX

2017

Dion, Johann; Deshayes, Frédérique; Storozhylova, Nataliya; Advedissian, Tamara; Lambert, Annie; Viguier, Mireille; Tellier, Charles; Dussouy, Christophe; Poirier, Françoise; Grandjean, Cyrille

Lactosamine-Based Derivatives as Tools to Delineate the Biological Functions of Galectins: Application to Skin Tissue Repair Article

ChemBioChem, 18 (8), p. 782–789, 2017, ISSN: 14397633.

Résumé | Liens | BibTeX

Dion, Johann; Advedissian, Tamara; Storozhylova, Nataliya; Dahbi, Samir; Lambert, Annie; Deshayes, Frédérique; Viguier, Mireille; Tellier, Charles; Poirier, Françoise; Téletchéa, Stéphane; Dussouy, Christophe; Tateno, Hiroaki; Hirabayashi, Jun; Grandjean, Cyrille

Development of a Sensitive Microarray Platform for the Ranking of Galectin Inhibitors: Identification of a Selective Galectin-3 Inhibitor Article

ChemBioChem, 18 (24), p. 2428–2440, 2017, ISSN: 14397633.

Résumé | Liens | BibTeX