Bakhtiary Zahra, Barar Jaleh, Aghanejad Ayuob, Saei Amir Ata, Nemati Elhameh, Ezzati Nazhad Dolatabadi Jafar, Omidi Yadollah
a Student Research Committee, Faculty of Pharmacy , Tabriz University of Medical Sciences , Tabriz , Iran.
b Research Center for Pharmaceutical Nanotechnology , Tabriz University of Medical Sciences , Tabriz , Iran.
Drug Dev Ind Pharm. 2017 Aug;43(8):1244-1253. doi: 10.1080/03639045.2017.1310223. Epub 2017 Apr 10.
Non-small cell lung cancer (NSCLC) patients with sensitizing mutations in the exons 18-21 of the epithelial growth factor receptor (EGFR) gene show increased kinase activity of EGFR. Hence, tyrosine kinase inhibitors (TKIs) such as erlotinib (ETB) have commonly been used as the second line therapeutic option for the treatment of metastatic NSCLC. While the ETB is available as an oral dosage form, the local delivery of this TKI to the diseased cells of the lung may ameliorate its therapeutic impacts. In the current study, we report on the development of ETB-loaded solid lipid nanoparticle (SLN) based formulation of dry powder inhaler (ETB-SLN DPI). ETB-SLNs were formulated using designated amount of compritol/poloxamer 407. The engineered ETB-SLNs showed sub-100 nm spherical shape with an encapsulation efficiency of 78.21%. MTT assay and DAPI staining revealed that the ETB-SLNs enhanced the cytotoxicity of cargo drug molecules in the human alveolar adenocarcinoma epithelial A549 cells as a model for NSCLC. To attain the ETB-SLN DPI, the ETB-SLNs were efficiently spray dried into microparticles (1-5 μm) along with mannitol. The ETB-SLN DPI powder displayed suitable flowability and aerodynamic traits. The Carr's Index, Hausner ratio and Next Generation Impactor (NGI) analyses confirmed deep inhalation pattern of the formulation. Based on these findings, we propose the ETB-SLN DPI as a promising treatment modality for the NSCLC patients.
表皮生长因子受体（EGFR）基因第18 - 21外显子发生敏感突变的非小细胞肺癌（NSCLC）患者，其EGFR激酶活性增强。因此，像厄洛替尼（ETB）这样的酪氨酸激酶抑制剂通常被用作转移性NSCLC治疗的二线治疗选择。虽然ETB有口服剂型，但将这种酪氨酸激酶抑制剂局部递送至肺部病变细胞可能会改善其治疗效果。在本研究中，我们报告了基于载有ETB的固体脂质纳米粒（SLN）的干粉吸入剂（ETB - SLN DPI）的研发情况。使用指定量的康普立糖/泊洛沙姆407制备ETB - SLN。所制备的ETB - SLN呈球形，粒径小于100 nm，包封率为78.21%。MTT法和DAPI染色显示，以人肺泡腺癌上皮A549细胞作为NSCLC模型，ETB - SLN增强了所载药物分子的细胞毒性。为了制备ETB - SLN DPI，将ETB - SLN与甘露醇一起高效喷雾干燥成微粒（1 - 5μm）。ETB - SLN DPI粉末表现出合适的流动性和空气动力学特性。卡尔指数、豪斯纳比和新一代撞击器（NGI）分析证实了该制剂的深吸气模式。基于这些发现，我们提出ETB - SLN DPI是NSCLC患者一种有前景的治疗方式。
