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Utilisation de la RMN pour la caractérisation structurale et cinétique d'associations peptide-liposome comme aide à la conception de formulation

Abstract : The encapsulation of active ingredients (AI) in liposomes is used in several domains such as pharmaceutical and cosmetic industries. Liposomes are drug delivery systems (DDS) used for a controlled release of AIs. To increase the efficiency of peptide drugs, I aim at designing optimized peptide/liposomes formulation by playing both on their composition and peptide structure. Potential parameters to be improved are their interactions, encapsulation efficiency and release kinetics. To reach this goal, I explored the potentiality of Nuclear Magnetic Resonance (NMR) spectroscopy to characterize peptides, liposomes and their behavior during release. The AIs used in this study are apelin-derived peptides that are of interest for homeostasis regulation of the cardiovascular system. Liposome and peptide structures as well as their interactions were characterized by ¹H and ³¹P NMR and cryo-EM. I showed that diffusion NMR methods that report on the apparent size of molecules can discriminate between the inner and the outer space of liposomes and for release quantification in-situ and in real-time without perturbing the process. Moreover, ¹H NMR spectra were used to monitor and quantify peptide release kinetics by spectral integration. I showed that the preparation method of liposomes drastically impacts their structure, release kinetics and interactions with peptides. Addition of a lipid chain increases the interaction with the liposomes, but the type and length of the chain induce only few differences. This approach could certainly be extended to other AIs and DDSs used for pharmaceutical and cosmetic applications.
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https://tel.archives-ouvertes.fr/tel-03200192
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Submitted on : Friday, April 16, 2021 - 12:03:14 PM
Last modification on : Thursday, May 6, 2021 - 10:50:57 AM

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Camille Doyen. Utilisation de la RMN pour la caractérisation structurale et cinétique d'associations peptide-liposome comme aide à la conception de formulation. Chimie analytique. Université Paris-Saclay, 2020. Français. ⟨NNT : 2020UPASS110⟩. ⟨tel-03200192⟩

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