The target of the current investigation was the delivery of oseltamivir phosphate (OSE) into the lung adenocarcinoma tissues by means of designing nanosized, non-toxic and biocompatible pegylated Eudragit based NPs and investigating their anticancer and antiangiogenic activity. The rationale for this strategy is to provide a novel perspective to cancer treatment with OSE loaded pegylated ERS NPs under favor of smaller particle size, biocompatible feature, cationic characteristic, examining their selective effectiveness on lung cell lines (A549 lung cancer cell line and CCD-19Lu normal cell line) and examining antiangiogenic activity by in vivo CAM analysis. For this purpose, OSE encapsulated pegylated ERS based NPs were developed and investigated for zeta potential, particle size, encapsulation efficiency, morphology, DSC, FT-IR, ¹H NMR analyses. In vitro release, cytotoxicity, determination apoptotic pathways and in vivo CAM assay were carried out. Considering characterizations, NPs showed smaller particle size, cationic zeta potential, relatively higher EE%, nearly spherical shape, amorphous matrix formation and prolonged release pattern (Peppas-Sahlin and Weibull model with Fickian and non-Fickian release mechanisms). Flow cytometry was used to assess the apoptotic pathways using the Annexin V-FITC/PI staining assay, FITC Active Caspase-3 staining assay, and mitochondrial membrane potential detection tests. Activations on caspase-3 pathways made us think that OSE loaded pegylated ERS NPs triggered to apoptosis using intrinsic pathway. As regards to the in vivo studies, OSE loaded pegylated ERS based NPs demonstrated strong and moderate antiangiogenic activity for ERS-OSE 2 and ERS-OSE 3, respectively. With its cationic character, smaller particle size, relative superior EE%, homogenous amorphous polymeric matrix constitution indicated using solid state tests, prolonged release manner, highly selective to the human lung adenocarcinoma cell lines, could trigger apoptosis intrinsically and effectively, possess good in vivo antiangiogenic activity, ERS-OSE 2 formulation is chosen as a promising candidate and a potent drug delivery system to treat lung cancer.

目前研究的目标是通过设计纳米尺寸、无毒和生物相容的聚乙二醇化 Eudragit 纳米粒子并将磷酸奥司他韦 (OSE) 递送到肺腺癌组织中，并研究它们的抗癌和抗血管生成活性。该策略的基本原理是为使用负载 OSE 的聚乙二醇化 ERS ​​NPs 的癌症治疗提供新的视角，有利于更小的粒径、生物相容性特征、阳离子特性，检查它们对肺细胞系（A549 肺癌细胞系和 CCD- 19Lu 正常细胞系）并通过体内检测抗血管生成活性CAM 分析。为此，开发并研究了 OSE 封装的聚乙二醇化 ERS ​​基 NPs 的 zeta 电位、粒径、封装效率、形态、DSC、FT-IR、¹ H NMR 分析。体外释放、细胞毒性、确定凋亡途径和体内进行了CAM测定。考虑到表征，NPs 表现出较小的粒径、阳离子 zeta 电位、相对较高的 EE%、接近球形、无定形基质形成和延长释放模式（具有 Fickian 和非 Fickian 释放机制的 Peppas-Sahlin 和 Weibull 模型）。流式细胞术用于评估凋亡途径，使用膜联蛋白 V-FITC/PI 染色测定、FITC 活性 Caspase-3 染色测定和线粒体膜电位检测测试。caspase-3 通路的激活使我们认为 OSE 负载聚乙二醇化的 ERS ​​NPs 使用内在通路触发细胞凋亡。至于体内研究表明，载有 OSE 的聚乙二醇化 ERS ​​的 NP 分别对 ERS-OSE 2 和 ERS-OSE 3 表现出强和中度的抗血管生成活性。具有阳离子特性，粒径较小，EE%相对较高，固态测试表明均质无定形聚合物基质构成，缓释方式，对人肺腺癌细胞系具有高度选择性，可内在有效地引发细胞凋亡，具有良好的体内抗血管生成活性，ERS-OSE 2 制剂被选为治疗肺癌的有希望的候选药物和有效的药物递送系统。