Nucleoside squalenization has been developed by Patrick Couvreur’s team (Institut Galien, Faculté de Pharmacie de Chatenay-Malabry) in 2006. This approach allows synthesizing aqueous suspensions of nanoparticles made of active principle through the simple and energy-cheap nanoprecipitation process.^1,2 These nanoparticles enable to reach a high encapsulation rate. They furthermore protect the active principle from a rapid degradation and allow targeting spatially and temporally its delivery.

The aim of our team in the Nanoprotection project is to study the structure and the future of Squalene-Adenosine (Sq-Ad) nanoparticles in biological media. Today, little is known on the structure of organic nanodrugs (liposomes, vesicles, nanoparticles…) in serum or cytoplasm. The main obstacle in characterizing the objects in situ comes from the similarity in terms of atoms and functions between them and the biological medium. An even higher degree of complexity is reached when the particles (like Sq-Ad NPs) are labile objects.

It is thus necessary to characterize Sq-Ad nanoparticles before and after their injection to fully control their preparation and understand their future in the organism. Our contribution is to develop strategies to monitor in vitro the structure and size distribution of nanoparticles in a model biological medium. We use our expertise in dispersed and complex media to specifically study these biologically active nanoparticles in biological media.^3–5   

Among the different available characterization techniques, Small Angle Neutron Scattering (SANS) enables to monitor density fluctuation at the nanometer scale. Recently, we have demonstrated the efficiency of this approach to follow the formation steps of other squalenoyl nanoparticles (Squalene-Gemcitabine and Squalene-Deoxytidine).⁶ We have thus explained the size-distribution control through solvent activity and the existence of an internal structure right from the first steps of formation.

We are building on these first results to study the structure of Sq-Ad nanoparticles and develop specific methodologies to monitor their evolution in model biological media. The first step consistd in monitoring the nanoparticles in a deuterated medium and then to deuterate a part of the Sq-Ad molecule to study it in a hydrogenated serum. In parallel, we study the specific interaction between Sq-Ad nanoparticles and chosen serum constituents (albumins, lipoproteins, etc.) with different spectroscopic and calorimetric techniques