Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS Deemed to be University, Mumbai, India.
Pharm Dev Technol. 2023 Oct;28(8):755-767. doi: 10.1080/10837450.2023.2251148. Epub 2023 Sep 4.
The study developed and evaluated Sorafenib Tosylate (SRT)-loaded polymeric microparticles (MPs) using biodegradable polymer polycaprolactone (PCL) as a potential inhalable carrier for NSCLC. MPs were prepared by spray-drying an oil-in-water (o/w) emulsion. The optimized MPs demonstrated excellent flowability, particle size of 2.84 ± 0.5 μm, zeta potential of -14.0 ± 1.5 mV, and 85.08 ± 5.43% entrapment efficiency. ATR-FTIR/DSC studies revealed a lack of characteristic peaks of the crystalline drug signifying good entrapment of the drug. MPs were spherical and uniform in SEM pictures. The MPs showed a biphasic release pattern up to 72h. The Anderson cascade impactor (ACI) investigation demonstrated the highest drug deposition at stage 4, which revealed that the MPs can reach the lungs' secondary and terminal bronchi. Inhalable MPs had an efficient aerodynamic property with a mass median aerodynamic diameter (MMAD) of 2.63 ± 1.3 μm, a geometric standard deviation (GSD) of 1.93 ± 0.2 μm, and a fine particle fraction (FPF) of 87 ± 2.5%. Finally, in cytotoxicity studies on A549 cancer cells, MPs had an IC value of 0.6011 ± 0.8 μM, which was 85.68% lower than free drug. These findings suggest SRT-loaded inhalable PCL-based MPs as a novel NSCLC treatment.
本研究开发并评估了索拉非尼甲苯磺酸盐(SRT)负载的聚合物微粒(MPs),使用可生物降解聚合物聚己内酯(PCL)作为潜在的可吸入载体用于非小细胞肺癌(NSCLC)。 MPs 通过喷雾干燥油包水(o/w)乳液制备。优化的 MPs 表现出优异的流动性、粒径为 2.84 ± 0.5 μm、Zeta 电位为-14.0 ± 1.5 mV 和 85.08 ± 5.43%的包封效率。ATR-FTIR/DSC 研究表明药物结晶的特征峰缺失,表明药物包封良好。 MPs 在 SEM 图片中呈球形且均匀。 MPs 在 72 小时内表现出两相释放模式。安德森级联撞击器(ACI)研究表明,在第 4 级药物沉积最高,这表明 MPs 可以到达肺部的二级和三级支气管。可吸入 MPs 具有高效的空气动力学特性,质量中值空气动力学直径(MMAD)为 2.63 ± 1.3 μm,几何标准偏差(GSD)为 1.93 ± 0.2 μm,细颗粒分数(FPF)为 87 ± 2.5%。最后,在 A549 癌细胞的细胞毒性研究中,MPs 的 IC 值为 0.6011 ± 0.8 μM,比游离药物低 85.68%。这些发现表明 SRT 负载的可吸入 PCL 基 MPs 作为一种新型 NSCLC 治疗方法。