Nano-in-microparticles used for inhalation lung cancer therapy combine the advantages of microparticles with aerodynamic diameters of 1∼5 μm for deep lung deposition and nanoparticles for long residence time in lung, high mucus penetrating and cancer cells uptake efficiency. In this work, nano-in-microparticles composed of chitosan nanoparticles and mannitol were prepared using a modified supercritical CO₂ assisted atomization (SAA-HCM) technique. Influences of process parameters of CO₂/liquid mass flow ratio, total mass concentration and nanoparticles/mannitol ratio on size and morphologies of nano-in-microparticles were investigated in detail. Well-defined spherical nano-in-microparticles with theoretical mass median aerodynamic diameter of 1∼2 μm were obtained under optimized conditions. Fraction of about 40 % of nanoparticles was redispersed in deionized water at nanoparticles/mannitol ratio of 10:90. Meanwhile, quick disintegration of nano-in-microparticles was observed under conditions simulating high humidity in lung. In summary, dissociation of nano-in-microparticles and redispersibility of nanoparticles were determined by the structure of nano-in-microparticles according to particles formation mechanism. This work will expand the applicability of SAA-HCM to the preparation of nano-in-microparticles from nanosuspension and provide more references for designing of particles with elaborate structures.

用于吸入型肺癌治疗的纳米微粒结合了以下优点：空气动力学直径为1至5μm的微粒可用于深部肺部沉积，而纳米微粒可在肺中停留时间长，黏液穿透力强和癌细胞吸收效率高。在这项工作中，使用改良的超临界CO ₂辅助雾化（SAA-HCM）技术制备了由壳聚糖纳米颗粒和甘露醇组成的纳米微粒。CO ₂工艺参数的影响/液体质量流量比，总质量浓度和纳米颗粒/甘露醇比例对纳米微粒的尺寸和形貌进行了详细研究。在优化的条件下，获得了定义良好的球形纳米微粒，其理论质量中位数空气动力学直径为1-2μm。将约40％的纳米颗粒的级分以纳米颗粒/甘露醇的比率为10∶90重新分散在去离子水中。同时，在模拟肺部高湿度的条件下，观察到纳米微粒的快速崩解。总之，根据微粒形成机理，通过微粒中的纳米结构来确定微粒中的纳米的离解和微粒的再分散性。