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

利用聚合物在超临界流体中自组装开发核酸药物纳米器件

基本信息

批准号：
16560664
负责人：
MISHIMA Kenji
金额：
$ 2.3万
依托单位：
Fukuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

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.

在本论文中，我们尝试利用超临界流体中聚合物的自组装来制备核酸药物。为了设计核酸药物，我们尝试在超临界CO_2（scCO_2）中通过高剪切混合形成高度分散的纳米颗粒-聚合物体系。据认为，这种混合技术将是一种有效的方法，用于生产分散良好，高负载的纳米颗粒-聚合物系统，而不使用表面活性剂和/或稳定剂。为了在超临界CO_2中获得高负载的TiO_2纳米颗粒-聚合物体系，使用了配备有柱状搅拌器和机械密封的高压容器。柱搅拌器将材料压向高压容器的内壁。搅拌器与内壁之间的剪切应力加速了纳米TiO_2在CO_2饱和聚合物悬浮液中的分散。将CO_2饱和的聚合物悬浮液快速膨胀至水相，得到聚合物微球。采用SEM、TEM、XRD等手段对微球的结构和形貌进行了表征。所得聚合物微球为高负载量的TiO_2-聚合物复合材料。通过提高搅拌器转速，增大高压釜中的剪切应力，可以提高聚合物颗粒中的TiO_2含量，并通过CO_2饱和聚合物悬浮液的快速膨胀制备L-聚乳酸（PLA）微球。在这项工作中，为了控制颗粒形态，将气体饱和的聚合物悬浮液通过喷嘴膨胀到水中。所获得的颗粒小于通过膨胀到大气中产生的颗粒。聚合物悬浮液在水中的膨胀阻碍了颗粒的生长和团聚。聚合物液滴和水相之间的界面张力有助于微球的形成。