Compréhension à l’échelle atomique des processus de libération de médicament dans des nanoMOFs par spectroscopie RMN in situ et relaxométrie

Allocation, AAP 2019

Project leader: Charlotte Martineau-Corcos

Abstract:

Nanoparticles (NPs) based on porous metal-organic frameworks (MOFs) are of growing interest in medicine, with applications for controlled drug delivery, targeting of diseased tissues/organs or in imaging. The high porosity of MOFs, their high specific surface and unrivalled versatility in terms of composition and easy functionalization, are the reasons why these materials are particularly appealing systems for loading of large amounts of therapeutic molecules.

The control over the MOF NP degradation in biological media is a key parameter as it in turn allows a better control of the drug delivery kinetics. If usual techniques (HPLC, etc) can provide data on the delivery, none of them allows an accurate description at the atomic scale of the nanoMOF and active principle ingredient evolution during degradation, the nature of the formed species and their influence upon drug release.

In this context, nuclear magnetic resonance (NMR), a non-destructive local technique, appears ideally suited to study these MOF NPs that lack long-range order. Analysis of solid-state NMR spectra provides information about the nature and quantity of the species, their coordination, dynamics and potential interactions. The NMR methods are nowadays well established for the study of host-guest interactions in porous solids. Now, we want to push the limits of our methods in order to be able to follow in situ and at the atomic scale the processes occurring during drug delivery from a MOF in a biological medium.

Evolution of the MOF NP porosity during drug delivery is also a parameter to take into account. Low field proton relaxometry, with water as probe molecule, is efficient to probe the porosity of porous polymer particles. However more information can be obtained using variable field NMR relaxometry. We plan here to explore the possibility of proton relaxometry to study the degradation processes of the loaded MOF NPs

Themes:

Towards modeling at all scales

Collaborations: