肺部给药用高分子多孔微球的研究进展

肺部给药制剂将药物直接递送于肺部组织, 可获得较高的局部浓度, 有利于肺部疾病治疗, 并可能减少药 物的全身不良反应, 因此成为许多肺部疾病治疗药物的优选, 但进入肺部的药物易被肺组织清除, 减少了药物的肺 内滞留时间, 影响疗效。较小粒径 (1～5 μm) 的颗粒虽然易被吸入肺深部, 但同时也易被肺巨噬细胞吞噬和清除; 较大几何粒径 (Dg > 5 μm) 和低密度 (ρ < 0.4 g·cm -3 ) 的高分子多孔微球 (porous polymer microspheres, PPMS) 不仅 能有效逃避肺泡巨噬细胞吞噬, 同时由于空气动力学直径合适, 其肺部有效沉积率高, 高分子可生物降解且无毒副 作用, 因此成为肺部给药载体的研究热点。本文结合颗粒肺部清除机制, 总结了 PPMS 的制备材料和方法, 以及其 质量控制等, 并对 PPMS 的发展提出见解, 为 PPMS 的深入研究提供参考。

Pulmonary drug delivery agents deliver drugs directly to the lung tissue to obtain higher local concentration, which is beneficial to the treatment of lung diseases, and may reduce the systemic side effects. Therefore, it has become the preferred drug for the treatment of many lung diseases. However, the drugs entering the lungs are easily cleared by the lung tissues, which reduce the retention time of the drugs in the lungs and affects the efficacy. Although particles with a smaller particle size (1-5 µm) are easily inhaled into the lungs, they are also easily swallowed and cleared by lung macrophages. While the porous polymer microspheres (PPMS) with larger geometric diameter (Dg > 5 µm) and low density (ρ < 0.4 g·cm^-3) can not only effectively avoid the phagocytosis of alveolar macrophages, but also have a high effective deposition rate in the lungs due to the appropriate aerodynamic diameter, moreover, the polymer is biodegradable and non-toxic, so it has become a research hotspot for pulmonary drug delivery carriers. This article combined with the lung clearance mechanism of granules, summarized the preparation materials and methods of PPMS, as well as its quality control, etc. Furthermore, opinions are also put forward for the development of PPMS, to provide a reference for the in-depth study of PPMS.