Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
Drug Dev Ind Pharm. 2020 Aug;46(8):1265-1277. doi: 10.1080/03639045.2020.1788063. Epub 2020 Jul 13.
Gefitinib as an epidermal growth factor receptor tyrosine kinase inhibitor has strong potential in lung cancer therapy. However, a major challenge of using gefitinib is its toxicities. In the present study, we developed a dry powder inhaler dosage form containing gefitinib loaded glucosamine targeted solid lipid nanopaticles (Gef-G-SLNs) to locally transfer anticancer agent to the lung tumor. The Gef-G-SLNs were prepared by emulsion-solvent diffusion and evaporation method and optimized with irregular factorial design. The optimized nanoformulation was tested for action against A549 cells. Mannitol or lactose based dry powders were obtained from Gef-G-SLNs after spray drying and characterized using Anderson Cascade Impactor. The optimized formulation had drug loading of 33.29%, encapsulation efficiency of 97.31 ± 0.23%, zeta potential of -15.53 ± 0.47 mV, particle size of 187.23 ± 14.08 nm, polydispersity index of 0.28 ± 0.02 and release efficiency of 35.46 ± 2.25%. The Gef-G-SLNs showed superior anticancer effect compared to free gefitinib. The increased cellular uptake of G-SLNs in A549 cells was demonstrated compared with non-targeted SLNs using flow cytometry and fluorescence microscopy. The produced mannitol based microparticles showed suitable aerodynamic properties with an acceptable mass median aerodynamic diameter of 4.48 µm and fine particle fraction of 44.41%. Therefore, it can be concluded that this formulation represents promising drug delivery to treatment of lung cancer.
吉非替尼作为一种表皮生长因子受体酪氨酸激酶抑制剂，在肺癌治疗方面具有很强的潜力。然而，使用吉非替尼的一个主要挑战是其毒性。在本研究中，我们开发了一种含有吉非替尼负载葡萄糖胺靶向固体脂质纳米颗粒（Gef-G-SLNs）的干粉吸入剂剂型，旨在将抗癌药物局部递送到肺癌肿瘤部位。Gef-G-SLNs 采用乳化溶剂扩散和蒸发法制备，并采用非规则析因设计进行优化。对优化后的纳米制剂进行了针对 A549 细胞的作用测试。喷雾干燥后从 Gef-G-SLNs 中获得了基于甘露醇或乳糖的干粉，并使用安德森级联撞击器进行了表征。优化后的配方具有 33.29%的载药量、97.31±0.23%的包封效率、-15.53±0.47 mV 的 zeta 电位、187.23±14.08nm 的粒径、0.28±0.02 的多分散指数和 35.46±2.25%的释放效率。与游离吉非替尼相比，Gef-G-SLNs 显示出更好的抗癌效果。与非靶向 SLNs 相比，通过流式细胞术和荧光显微镜证明了 A549 细胞中 G-SLNs 的细胞摄取增加。所产生的甘露醇基微球显示出合适的空气动力学特性，可接受的质量中值空气动力学直径为 4.48μm，细颗粒分数为 44.41%。因此，可以得出结论，该制剂代表了一种有前途的肺癌治疗药物传递系统。
