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Contexte
Dispersions of nanodroplets are increasingly used as contrast agents in medical imaging and as drug carriers. We are particularly interested in the stability of original nanoemulsions composed of perfluorocarbon nanodroplets stabilized by fluorinated surfactants and dispersed in aqueous solvents. After intravenous injection, such nanoemulsion can be used as contrast agents for 19F MRI or ultrasound imaging as well as drug-carriers for targeted therapeutic.
For medical imaging and targeted therapeutic applications nanodroplets must remain sufficiently stable to allow storage and, once injected, accumulation of droplets at the targeted site. The main goal of this project is to determine the best conditions leading to nanoemulsions stable over several days in conditions mimicking in vivo medium, and over several months in solvent for storage purpose. The time evolution (i.e. aging) of our nanodroplets strongly depends on the initial droplet size distribution, the type of surfactant used to encapsulate the perfluorocarbon present in their core and of the main processes involved in aging behavior, that is: coalescence of droplets and/or to the diffusion of droplet molecules through the solvent (Oswald ripening). The relation between these processes and droplet properties, in particular surfactant properties, is still unclear. It is even worse when additional oil is added into the droplet core to allow the solubilization of drugs.
Projet
In this project we propose to study the process of nanoemulsion aging by varying the droplet components using experimental and simulation approaches.
Experimental approaches will consist in the study of the variation with time of mean size and size distribution of the droplets using either an apparatus based on the Coulter effect or a dynamic light scattering system. Among the surfactant properties, we will be interested to measure its interfacial tension (using the drop method) and its proportion to coalescence (using microfluidics).
Simulations, conducted in order to reproduce the experimental data and understand the underlying mechanisms, will be performed using two different approaches. Either using a program called Emulsion Estability Simulations that predicts the changes in size of droplet distribution or software basd on the Lattice-Boltzmann method.
These studies will be performed at first in solutions, where only droplets are present. Then, experiments will continuously be made more sophisticated in order to mimic more precisely the in vivo conditions (addition of plasma protein such as serum albumin, confinement…).