针对高效制备单分散聚合物纳米水凝胶微球手段欠缺问题, 我们发展了一种新型的纳米水凝胶微球制备新技术——回流沉淀聚合技术, 与以往的沉淀聚合及蒸馏沉淀聚合相比, 该方法效率更高、普适性更强、操作更简单, 适合高效制备单分散的纳米水凝胶微球及其复合微球. 通过考察制备聚甲基丙烯酸微球过程中的反应时间、固含量、交联剂含量、混合溶剂比例等影响因素, 成功制备了形态可控、尺寸均一、水中分散性良好的聚甲基丙烯酸纳米水凝胶微球, 并给出了微球形态控制的基本规律. 通过该技术制备的纳米水凝胶微球及其复合微球将被广泛用于生物医用材料中.

Monodisperse polymer microspheres have been widely used in chromatography separation, coating additives, biological separation and targeted drug delivery due to their varying properties, such as the various morphology, well-defined composition, functional surface and biocompatibility. Recently, the preparation of monodisperse polymer microspheres and nanohydrogels has attracted great interests. Considering the shortage of the preparation method of the polymer nanohydrogels, we developed a new technique—reflux precipitation polymerization—for preparation of monodisperse and biocompatible polymer nanohydrogels. A typical procedure for the reflux precipitation polymerization is described as follows: Firstly, a suitable amount of monomers[MAA (methacrylic acid) and DVB (divinylbenzene)] and initiator[AIBN (2,2-azobisisobutyronitrile)] dissolved in acetonitrile was added into a round-bottom flask configured with a condenser. When the reaction temperature increased to the boiling point of the solution for about 5 min, the initially transparent reaction solution became milky white, and the reaction was continued for another 2 h. Then the resultant microspheres were separated and purified by repeating ultra-centrifugation (12000 r/min for 3 min)-decanting-redispersion (in ethanol with ultrasonic bathing) for three times. The morphology and particle size distribution of PMAA nanohydrogels were characterized by scanning electron microscope (SEM) and dynamic light scattering (DLS). Compared to the traditional precipitation polymerization and distillation-precipitation polymerization, this new method has many merits, such as high efficiency, good repeatability and easy operation, which can be used to high efficient preparation of polymer nanohydrogels and the related composite microspheres. Through testing the reaction conditions, such as reaction time, solid content, cross-linker content and solvent mixture, we successfully prepared the monodisperse PMAA nanohydrogels, and obtained the fundamental rule for the morphology control. We found that the diameter of PMAA nanohydrogels became larger and larger as the reaction time extended or the solid content and/or the ratio of good solvent of polymer increased. The particle size distribution of the PMAA nanohydrogels became poor if the solid content or the cross-linker content was beyond a certain threshold. These nanohydrogels and the related composite microspheres prepared by this new technique will be widely used in the biomedical fields.