ABSTRACT
The synthesis, characterization and inclusion in liposomes of a glucosylated bolaamphiphile built on a calix[4]arene scaffold are described. The new glucocalixarene bolaamphiphile destabilizes bilayers of saturated lipids whereas it rigidifies those of unsaturated lipids, thus reducing leakage of calcein from the liposome internal aqueous compartment. Moreover, from fluorescence and turbidimetry experiments it was found that the glucose units of bolaamphiphile 1 functionalised liposomes allow a specific multivalent interaction with the tetrameric glucose binding protein Concanavalin A. These results therefore represent a novel strategy to functionalise liposomes with saccharides, exploiting multivalent glycosylated ligands to be used in the preparation of drug delivery systems potentially able to target specific lectins.
Subject(s)
Calixarenes/chemistry , Furans/chemistry , Glucose/chemistry , Lectins/chemistry , Lipid Bilayers/chemistry , Phenols/chemistry , Pyridones/chemistry , Concanavalin A/chemistry , Drug Delivery Systems , Liposomes/chemical synthesis , Liposomes/chemistry , Models, Molecular , Molecular StructureABSTRACT
Previous investigations showed that the extent of DNA condensation and the efficiency in the transfection of liposomes formulated with 1,2-dimyristoyl-sn-glycero-phosphocholine and cationic stereomeric gemini surfactants depend heavily on the stereochemistry of the gemini. The influence of the stereochemistry on the interaction of lipoplexes with zwitterionic and anionic cell membrane models was investigated by differential scanning calorimetry to rationalize their different biological behavior. Further, the thermotropic behavior of the corresponding liposomes and of the spontaneous self-assemblies of gemini surfactants in the presence and in the absence of DNA was evaluated to correlate the physicochemical properties of lipoplexes and the stereochemistry of the cationic component. The obtained results show that the stereochemistry of the gemini surfactant controls lipoplexes organization and their mode and kinetic of interaction with different cell membrane models.
