Abstract

The present hypothesis was to identify the potential of sorafenib tosylate (ST) loaded liposomal dry powder inhaler (ST-LDPI) for targeting non-small cell lung cancer (NSCLC). ST-LDPI was obtained by spray drying the ST loaded liposomes, evaluated for physicochemical properties and in vitro lung deposition by Andersen Cascade Impactor (ACI). Optimized liposomal formulation showed the particle size, zeta potential, encapsulation efficiency and drug content of 111.15 ± 1.03 nm, −29.87 ± 0.56 mV, 93.13 ± 1.11% and 84.47 ± 1.28%, respectively. Furthermore, ST-LDPI exhibited low density and good flowability. FESEM confirmed the spherical nature of particles with mean size of 3.15 ± 0.51 μm. The DSC and FTIR spectra revealed complete encapsulation of ST. Further, the PXRD showed reduced crystallinity ST. In vitro deposition demonstrated the fine particle fraction of 83.7 ± 0.09%, recovery of 95.43 ± 0.03%, mean mass aerodynamic diameter 3.15 ± 0.2 µm, geometric standard deviation 1.78 ± 0.15 µm and 85 ± 0.1% dispersibility. The In vitro drug release revealed biphasic release pattern, burst release in the first 6 h followed by sustained release up to 72 h. Hence this novel approach could be a targeted delivery of ST to the NSCLC treatment.

摘要

目前的假设是确定装载甲苯磺酸索拉非尼 (ST) 的脂质体干粉吸入器 (ST-LDPI) 用于靶向非小细胞肺癌 (NSCLC) 的潜力。ST-LDPI 是通过喷雾干燥装载 ST 的脂质体获得的，通过 Andersen Cascade Impactor (ACI)评估理化性质和体外肺沉积。优化后的脂质体配方的粒径、zeta 电位、包封率和药物含量分别为 111.15 ± 1.03 nm、-29.87 ± 0.56 mV、93.13 ± 1.11% 和 84.47 ± 1.28%。此外，ST-LDPI 表现出低密度和良好的流动性。FESEM 证实了平均尺寸为 3.15 ± 0.51 μm 的颗粒的球形性质。DSC 和 FTIR 光谱显示 ST 完全包封。此外，PXRD 显示出降低的结晶度 ST。体外沉积表明细颗粒分数为 83.7 ± 0.09%，回收率为 95.43 ± 0.03%，平均质量空气动力学直径为 3.15 ± 0.2 µm，几何标准偏差为 1.78 ± 0.15 µm，分散性为 85 ± 0.1%。的体外药物释放前6小时，然后持续释放达72小时显示双相释放模式，突发释放。因此，这种新方法可能是将 ST 靶向递送至 NSCLC 治疗。