Development of Nanodevice for Nucleic Acid Drugs Utilizing Self-Assembly of Polymer in Supercritical Fluids

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In this work, we attempt the formation of nucleic acid drugs utilizing self-assembly of polymer in supercritical fluids. To design the nucleic acid drugs, we try the formation of a highly dispersed nanoparticle-polymer system by high shear mixing in supercritical CO_2(scCO_2). It was considered that this mixing technology would be an effective method for the production of a well dispersed, highly loaded nanoparticle-polymer system, without the use of surfactants and/or stabilizers. In order to obtain highly loaded TiO_2 nanoparticle-polymer systems in scCO_2, a high-pressure vessel equipped with a column agitator and mechanical seal was used. The column agitator forces materials to the inside wall of the high-pressure vessel. The shear stress between the column agitator and the inside wall accelerates the dispersion of TiO_2 nanoparticles in CO_2 saturated polymer suspensions. After rapid expansion of the CO_2 saturated polymer suspensions to an aqueous phase, polymer microspheres were obtained. The structure and morphology of the microspheres were investigated by SEM,TEM, and XRD. The polymer microspheres obtained were highly loaded TiO_2-polymer composites. The TiO_2 content in the polymer particles was increased by an increase in the rotational speed of the agitator, and consequently the shear stress in the high-pressure vessel.Furthermore, L-poly(lactic acid)(PLA) microspheres were produced by rapid expansion of CO_2 saturated polymer suspensions. In this work, to control the particle morphology, the gas saturated polymer suspensions were expanded through the nozzle to water. The obtained particles were smaller than those produced by expansion to atmosphere. The expansion of polymer suspensions to water impedes particles growth and agglomeration. The interfacial tension between the polymer droplets and water phase contributes the microspheres formation.