ED Sciences Chimiques
A new generation of bolaamphiphiles for sustained drug delivery: design, synthesis and proof-of-concept validation
by Khaled AL YAMAN (Institut de Chimie & de Biologie des Membranes & des Nano-objets)
The defense will take place at 10h00 - Salle de conférence de l'IECB IECB, 2 rue Robert Escarpit, 33607 PESSAC
in front of the jury composed of
- Isabelle BESTEL - Professeure - Université de Bordeaux - Directeur de these
- Edouard BADARAU - Maître de conférences - Université de Bordeaux - CoDirecteur de these
- Tina KAUSS - Professeure - Université de Bordeaux - Examinateur
- Pascal MARCHAND - Professeur - Université de Nantes - Examinateur
- Basile PERES - Maître de conférences - Université Grenoble Alpes - Rapporteur
- Monique MATHÉ-ALLAINMAT - Chargée de recherche - Nantes Université - Rapporteur
The efficiency of liposomes as nanocarriers has been drastically compromised by their stability issues. Targeting passive diffusion of therapeutics from liposomes is the current focus for identifying next-generation long-acting delivery systems. Drug delivery using bolaamphiphiles as key formulation components can reveal interesting for the design of stable nanocarriers. However, one of the major limitations is the propensity of the bola molecules to deliver planar membranes that are devoid of any drug delivery properties. The present manuscript describes the design and synthesis of a novel class of bolaamphiphiles to be used in a formulation recipe, in mixture with natural phospholipids, with the aim of controlling the drug release properties from the resultant liposomes. The chemical pattern of the newly designed bolas is built on two natural phospholipids. However, contrary to the bola derivatives previously reported in literature, a key structural modification was incorporated: the two natural phospholipids are linked through a polar moiety. Molecular dynamic simulations of these systems highlighted the key role of the polar linker in the generation of two extreme conformations: an extended and a bent one. While the extended conformer contributes to the membranes' rigidity, the bent conformer stabilizes the high curvature of the induced bolasomes. The preliminary data showed the ability of this synthetic bolaamphiphiles to induce spherical nanoparticles independently of the addition of any excipients, when formulated alone or mixed with classical phospholipids. The newly synthesized bola vesicles were characterized by differential scanning calorimetry, dynamic light scattering, transmission electron microscopy, size exclusion chromatography, fluorimetry, and coarse-grained molecular dynamics. Through the library of the synthesized bolalipids, one bola derivative was identified to promote a sustained-release profile of the incorporated hydrophilic cargo. This opens the way for a new strategy to tackle long-term drug delivery systems to be used in clinics for treating chronic diseases and in cancer therapy.
ED Sociétés, Politique, Santé Publique
The dead, a public problem ?
by Alèxe DUVAUT (Centre Emile Durkheim)
The defense will take place at 14h00 - Salle Copernic Sciences Po Bordeaux, 11 allée Ausone, 33600 Pessac
in front of the jury composed of
- Laurie BOUSSAGUET - Professeure des universités - Université de Rouen / Sciences Po Paris - Examinateur
- Emmanuel HENRY - Professeur des universités - Université Paris Dauphine - PSL - Rapporteur
- Gaelle CLAVANDIER - Professeure des universités - Université Jean Monnet Saint-Etienne - Rapporteur
- Gilles PINSON - Professeur des universités - Sciences Po Bordeaux/Université de Bordeaux - Examinateur
By studying representations of public service and the narratives of actors from the “mortuary chain” - defined as an architecture of actors who share the various competencies inherent in the disposal of the deceased at any given time - as well as observations within funeral organizations and institutional documentation, this research contributes to shedding light on the construction of policies that frame the care of the deceased, from death to burial. Drawing on the analysis of ‘public problems', it questions the organizing capacity of the notion of public service in terms of the construction of public action and the emergence of such problems. The treatment of the data, based on a variety of statistical tools and an analytical grid rooted in the study of public problems, aims to go beyond the quantitative/qualitative opposition. The main argument of the thesis is that the notion of public service constitutes an inescapable value within the narration of public problems linked to the mortuary chain. The appropriation and translation of the notion by different actors, enrolled in combats for their position and legitimacy, explains the emergence of public problems. Between these cognitive matrices, the symbolic dividing lines reflect the state of jurisdictional struggles that underpin the architecture of the mortuary chain. The study of the political work of issue promotors sheds light on the conditions under which policy is fabricated at different scales and enables us to understand who governs the care of the dead at different scales. One result is to highlight a certain form of autonomy of political scales, and the coexistence of different regimes of public debate, more or less discrete and concentrated in the hands of owners who work to perpetuate institutions of power. Finally, through the study of identified public problems such as the price of funerals, and the “non-problem” of confessional areas, this research provides an understanding of how the management of the dead is organized at local and national levels in France, and more generally sheds light on the epistemological status of the vague notion of public service through the study of a singular sector, the mortuary chain.