Submicron cationic emulsions as a new delivery system for oligonucleotides

Purpose. The main purpose of the present study was to investigate submicron emulsions as potential oligonucleotide (ON) delivery system. Methods, Submicron emulsions containing various concentrations of stearylam ine (SA) were prepared by microfluidization. After association with model o ligothymidylates, these emulsions were characterized in terms of particle s ize, zeta-potential, association efficiency and release upon dilution. The interactions between ON and SA were investigated by partitioning studies be tween water and oily phases, with ON of three different lengths (pdT(16), p dT(30), pdT(50)). The stability of pdT(16) in the presence of nucleases was evaluated by incubation in cell culture medium supplemented with 10% of fo etal calf serum. Results. The ON association efficiency was much higher with emulsions conta ining SA (E-SA) than with control emulsions (E-0), whatever the ON length. In addition, E-SA was shown to protect ON against degradation For up to 3 h ours in culture medium. ON and SA were able to form ion-pairs and the resul ting complex was found to be insoluble both in water and in oil. Zeta poten tial was maintained constant when increasing the ON concentration, until fl occulation occurred (up to 250 mu M in the case of pdT(16) for example). Th is has been explained by the presence of SA in excess, soluble in the oily core of droplets, able to migrate towards the interface and replacing SA ne utralized in ion-pairs. Conclusions. E-SA appears to be a valuable system for delivery of ON and mi ght even be improved by selecting an oily phase in which the SA/ON complex would be soluble.