叶酸靶向多西紫杉醇纳米肺吸入粉雾剂的制备及评价

Preparation and evaluation of inhaled dry powders based on folic acidconjugated Docetaxel nanoparticles

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。

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 evapora- tion 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. MTY assay was employed to study the cytotoxicity and tumor-targe- ting 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 （0） 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 appli- cation by achieving higher anti-cancer activity in tumor site and lower damage to healthy organs.