Télécharger le sujet complet au format pdf
Contexte
All drugs come with side effects. They are due to the presence of huge amounts of drug in the patient body necessary to locally reach the minimum concentration needed for the drug to take effect. To alleviate this problem, drugs can be encapsulate into custom-made carriers, which function is to bring drugs to the site to be treated, then to deliver them. We have developed such carriers made of a mixed fluorocarbon/oil nanodroplets encapsulated into a fluorinated surfactant shell. The perfluorocarbon allow the droplets to act as contrast agent for both echography and 19F MRI. The oil allows the solubilization of hydrophobic drugs. Alternatively, we have developed fluorinated drugs that can be directly solubilized in the fluorocarbon droplet core, thus removing the need of oil. The nanometric size let these droplets to escape into surrounding tumor tissues from veins and concentrate in the vicinity of targeted tumor.
Projet
In this project we aim at triggering the drug delivery by ultrasound using an experimental set-up that already exists in our laboratory. The delivery can be achieved either through the generation of cavitation, that will destabilize the droplet and allow the drug delivery, or by vaporizing the droplet into a microbubble. The last option offers the advantage to significantly increase the echogenicity of the object and it represents an ideal marker to assess the effectiveness of drug delivery. Both mechanisms will be studied as a function of the type of perfluorocarbons and of surfactants used for the droplet, as well as a function of droplet diameter and interfacial tension that are known to be important factors in droplet vaporization.
The optimum ultrasonic parameters to perform the drug delivery should also be determined. According to the experimental results the emulsion constituents will be modified accordingly to increase the efficiency of drug release. Indeed a novel analytical model, based on the results of our experiments, predicts the droplet vaporization from the droplet physical properties.
Finally, in vivo studies will be conducted either in our laboratory for ultrasound drug-delivery combined with echography or in an european partner of our EuroNanoMed II grant for ultrasound drug-delivery combined with 19F MRI.