Nanoprecipitation for nanomedecine: formation and stability of the nanoparticles

International audienceDispersed nanostructured liquid crystalline materials are promising candidates for drug delivery and other pharmaceutical applications. They can be easily formed from nanoprecipitation or solvent shifting methods with amphiphiles, however the mechanism of their formation and their stability with time are still under debate. A particular case of such nanostructures was introduced in 2006 by Couvreur et al. They take benefit of the amphiphilic properties of conjugates formed by the covalent link between a squalene moity and a drug (or a nucleosides) to form such dispersions. The high loading capacity of these nanoparticles and their specific structure induces a large improvement of their therapeutic efficacy in comparison to the single drug. To improve the use of these nanoparticles in drug delivery, a deeper understanding of the mechanism of formation could provide the keys for a better control over size distribution and stability. After a short summary on nanoprecipitation and solvent shifting methods, this presentation will focuses on the Squalenoyl based nanoparticles formation. Size and structural analysis by Small Angle Neutron Scattering revealed the paramount role of the solvent on the control of size 3 and the effect of the formulation parameters

Self-assembled nanostructured material: Mechanism of formation

International audienceIn memory of Isabelle, I choose 4 projects realized with her to illustrate how SANS can be used to determine the structure and the kinetic evolution of self-assembled nanostructured materials. In mesostructured materials made of organic surfactant (CTAB) and inorganic materials (ZrO2), SANS kinetic experiments (with a stopped-flow coupled to SANS) permitted to identify the role played by the micelles during the precipitation stages of the mesotructured material. Thanks to the H/D contrast, the organic part of the hybrid material in formation can be probed by SANS. Beyond these first stopped-flow experiments, SANS is the technique of choice to characterize the organic structure in hybrid systems. We used SANS to identify the structure of the surrounded CTAB bilayers around gold nanorods dispersed in water solution. SANS is also a powerful technique to characterize self-assembling squalene based nanoparticles used for nanomedecine. SANS revealed that particles size is controlled by the solvent composition (ethanol-water) after nanoprecipitation process. SANS also help to identify the specific interaction between these nanoparticles and fetal bovine serum (FBS) and bovine serum albumin (BSA), the main protein of blood plasma. In the particular case of squalene-adenosine (SqAd) nanoparticles (whose neuroprotective effect has been demonstrated in murine models ), we identify from a coupling of different techniques (SANS, Cryo-TEM, circular dichroism, steady-state fluorescence spectroscopy and isothermal titration calorimetry) that serum albumin partially disassembles SQAd nanoparticles with the formation of complex between BSA and SqAd monomers extracted from the nanoparticles. In each of these examples, SANS was a key technique to follow the transformation of the organic part in self-assembling nanostructured materials