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Nano-emulsions for drug delivery and biomedical imaging

PI : Nicolas Anton 

Nano-emulsions consist of a suspension of liquid nano-droplets from 20 to 300 nm stabilized by surfactants. Nano-emulsions are very stable in suspension, their formulation and characterization are very simple, and simply transposable for industrial scaling-up. The droplet’s core (generally oil) allow solubilization and nano-encapsulation of drugs, contrast agents, imaging probes (etc.) at very high concentrations. Eventually, high stability, high encapsulation efficiency and absence of toxicity makes nano-emulsions a very powerful and promising systems for numerous applications like drug delivery system and nano-contrast agent. Nano-emulsions can also serve as template for the generation of polymeric nanocapsules or nanoparticles.

Based on the theoretical physicochemistry of colloids and interface, with the aim of understanding and optimizing the nano-emulsion formulation processes, the group has developed a recognized expertise in the field of nano-emulsions and related systems.

Nano-emulsions as contrast agent

Over the last years, our group has developed several efficient formulations of nano-emulsion-based contrast agents for preclinical X-ray imaging (micro computed tomography, microCT). Actually the main problem with the use of clinical X-ray contrast agents for preclinical imaging (i.e. small iodinated hydrophilic molecules) is their very fast blood clearance by kidney, thus potentially inducing renal toxicity. The idea is to increase the size of the contrast agent (> 50 nm) to prevent this glomerular filtration and thus allowing a long lasting contrast in blood pool or specific organs.

The strength of nano-emulsions lies in their high encapsulation properties (e.g. of iodine), their good physiological properties (pH, osmolarity) and low toxicity, their surface functionalization. A representative example of such formulation is published here : DOI = 10.1016/j.biomaterials.2012.09.026

Nano-emulsions for multimodal imaging

Nano-emulsions are also very suited for encapsulating fluorescent probes at high concentrations, thus enabling a multimodal imaging. We have shown that it is possible to obtain ultrabright nano-droplets avoiding fluorescence self-quenching and dye leakage (see publication here : DOI = 10.1039/C2RA21544F). This can be performed using classical dyes derivatives, like Nile Red. Actually, we disclosed that in living animal model (zebrafish) classical Nile Red encapsulated in nano-emulsions shows a strong release towards the surrounding tissues, whereas modified Nile Red (lipophilic Nile Red) does not leak and allows accurate imaging of the blood.