CYCLODEXTRINES: FROM THE INCLUSION TO NANOSTRUCTURED SYSTEMS

L. Mauclaire 

CEA-DSM-DRECAM-SCM    CEA/Saclay F-91191 Gif sur Yvette cedex (France)

Cyclodextrines are cyclic oligosaccharides. They are constituted by units of glucose connected by a 1-4 bound. These macromolecules have a shape of tore or bottomless goblet. This structure confers particular properties on these molecules because cyclodextrines possess a hydrophobic internal cavity and a hydrophilic external surface. This particularity allows to envisage the inclusion of hydrophobic compounds in the cyclodextrines (Host-guest concept) This inclusion capacity allows the solubilization of hydrophobic compounds in aqueous solution. 
In this presentation, we shall present some applications obtained from the cyclodextrine derivates. Among these:
1-	The solubilization of a radiolabeled fatty acid by a modified cyclodextrine. From this result, we were able to establish a new formulation for this radiopharmaceutical. The use of the cyclodextrine, allowed an operation of sterilisation of this new preparation. Also, we shall show the in vivo evolution of the complex. 
2-	The grafting of an "antenna" on a cyclodextrine allows to transport the cyclodextrine to a specific organ or tissue rich in the receptor for this antenna. This has been assayed, for example, by grafting on cyclodextrines a neuropeptide (substance P or SP). It has been demonstrated the hybrid compounds fully retain their inclusion properties towards hydrophobic guests. Further studies in vitro with cells enriched in receptors for SP and in vivo on rats have evidenced a adducts full recognition by the receptors of SP.
3-	The combination of the properties of classical transporters (such as liposomes) with the versatility and specificity of cyclodextrines and derivatives leads to the availability of original objects. This is obtained by grafting a highly hydrophobic moiety on the cyclodextrine. According to the nature of the polar head (cyclodextrine) and of the lipophilic moiety, the amphiphilic derivatives can either insert into model membranes or form spontaneously micelles as shown on figure 1. These are able to solubilize lipids of natural cell membranes and can be used to isolate and/or inactivate membrane proteins or to remove a toxic agent. 

Figure 1 : Example of a micelle formed by a cholesteryl-cyclodextrine derivative