叶酸靶向多西紫杉醇纳米肺吸入粉雾剂的制备及评价

目的: 制备基于叶酸靶向多西紫杉醇纳米粒的肺吸入粉雾剂，用于肺癌的治疗。方法: 采用有机溶剂挥发法制备叶酸靶向纳米粒，考察纳米粒理化性质，溴化噻唑蓝四氮唑（MTT）实验法研究纳米粒的体外细胞毒性和肿瘤细胞叶酸靶向性，使用喷雾干燥技术进一步制备基于纳米粒的肺吸入粉雾剂，并考察其理化性质。 结果: 本实验制备的叶酸靶向纳米粒粒径为（100.1±1.0） nm，普通纳米粒组IC50为（2.09±0.82） μmol/L，叶酸靶向纳米粒组IC50为（0.80±0.32） μmol/L。肺吸入粉雾剂体外沉积率和休止角分别为（21.10±0.18）%和（36.75±0.52）°。结论: 成功制备了基于叶酸靶向纳米粒的肺吸入粉雾剂，肺部吸入抗癌药物直达病灶部位，主动靶向肺癌细胞，提高靶器官药物浓度，降低毒副作用，提高患者的顺应性，满足临床肺癌治疗所需。

Preparation and evaluation of inhaled dry powders based on folic acid-conjugated Docetaxel nanoparticles

AIM: To prepare docetaxel-loaded folic acid-conjugated nanoparticles (NPs-DTX-FA) for the treatment of lung cancer. METHODS: The NPs-DTX-FA were prepared by the solvent evaporation method and the nanoparticles (NPs) were then co-spray dried with excipients to obtain inhaled dry powders. The physiochemical properties of NPs and inhaled dry powders were evaluated. MTT assay was employed to study the cytotoxicity and tumor-targeting property of the NPs. RESULTS:The diameter of LPs-DTX-FA was （100.1±1.0） nm, the IC50 for NPs-DTX and NPs-DTX-FA were （2.09±0.82） μmol/L and （0.80±0.32） μmol/L, respectively. The fine particle fraction (FPF) and angle of repose (θ) of the inhaled dry powders were （21.10±0.18）% and （36.75±0.52）°, respectively. CONCLUSION: The preparation of NPs-DTX-FA based inhaled dry powders was successful and this formulation represented a possibility of clinical application by achieving higher anti-cancer activity in tumor site and lower damage to healthy organs.