Thèses

Lundi 30 Septembre 2024 à 14h00.

Development of Chelating Polymers to Protect Against Heavy Metal Exposure

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Directeur de thèse / thesis director :
Olivier Tillement et Francois Lux

Membres du jury / jury members :
Sylvie Begin-Colin
Ghislain David
Philippe Cassagnau
Cecile Vignal
Thomas Brichart (invited)
Laurent David (invited)

Résumé / Abstract :

This Ph.D. covers the topic of development of a chelating polymer to combat heavy metal exposure, notably the exposure by ingestion. Low level heavy metal contamination within food products is directly related to the many years of industrial pollution and is unfortunately found around the world. These metals within the human body are strongly associated with chronic kidney disease and kidney failure, cardiovascular diseases, neurodegenerative diseases, and cancer. Classified as a chronic exposure, there is no reliable treatment that exists today for ingestion exposure; it is therefore crucial to explore new therapeutic ideas limiting the consequences of progressive accumulation of these metals within the body, especially for the at-risk populations. The Ph.D. work was based on a naturally occurring biopolymer: chitosan. During this Ph.D. work, the polymer was functionalized with chelating molecules, as well as characterized, studied, and compared between themselves to find the best functionality to target lead and cadmium specifically. The fight against chronic exposure to lead and cadmium, especially by ingestion via an oral exposure, can be imagined with an oral medication. This functionalized polymer in the form of an oral medication responds to the following criteria: retention within the gastrointestinal tract without penetrating into the bloodstream, elimination of heavy metals at low concentrations without disturbing the homeostasis of other essential metals, and a total elimination from the gastrointestinal system in a short time period. This multidisciplinary research covers various fields from fundamental analytical chemistry for the characterization of the physical and chemical properties of the polymers to in vivo analyses (biodistribution, hematological, and histopathological) to evaluate the efficacy of the medication, and finally, a proof of concept showing the feasibility of its pharmaceutical formulation.

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