Roselyne Dirson

SYNTHESIS AND CHARACTERIZATION OF SUPRAMOLECULAR BIOVECTOR (SMBV) SPECIFICALLY DESIGNED FOR THE ENTRAPMENT OF IONIC MOLECULES

Supramolecular biovectors (SMBV) are nanoparticular drug carriers composed of an internal crosslinked solid core externally grafted with fatty acids and surrounded with a phospholipid layer. We show in this paper that the internal core can be derivatized with anionic ligands such as phosphate in order to allow the efficient entrapment of cationic molecules through a process akin to ion exchange. Synthesis of SMBV involved first a cross linking and derivatization step of polysaccharides followed by a homogenization, a drying and a regioselective acylation step. Acylated polysaccharide cores are thus obtained which can be loaded with drugs and wrapped with a phospholipid layer. The SMBVs obtained are characterized through their size, 20 nm, and their ability to filter through 0.22 microns pore size membrane. Gel permeation chromatography experiments performed with various phospholipid/acylated cores ratios indicate that SMBVs form entities distinct from liposomes and that the optimum phospholipid/acylated cores ratio for this specific type of SMBVs is close to 100%. The supramolecular structure of SMBVs and in particular the spatial proximity between acylated cores and phospholipids is demonstrated through resonance energy transfer experiments. The drug loading capability of SMBVs is illustrated by the preparation of gentamicin and doxorubicin loaded SMBV. The therapeutic potential of SMBVs is then discussed notably in the light of a possible biomimetism with low density lipoproteins (LDL).