中文摘要：

本文探索构建一种具有脂质-二氧化硅一脂质复合结构的纳米载体，作为可共载多种药物用于抗肿瘤联合治疗的口服递药系统。以具有广谱抗肿瘤活性并为P糖蛋白（P．gP）底物的紫杉醇和P-gp抑制剂环孢素作为模型药物对。并对该给药系统进行制备工艺优化、理化性质与体外释放特性考察、药动学、药效学以及载体安全性系统评价。结果表明，所得共载紫杉醇与环孢素的给药系统制备方法条件温和，操作简易、可控，所得制剂平均粒径为（100．2±15．2）nm，多分散系数（PDI）为0．251±0．018，其对紫杉醇和环孢素的平均包封率分别为（90．15±2．47）％和f80．64±3．52）％。体外释药初步显示环孢素先于紫杉醇释放的序贯释放趋势。体内药动学结果表明，此共载制剂显著提高紫杉醇经口服吸收（相对单一紫杉醇脂质体的相对生物利用度为405．27％）。在体内药效学中表现为显著抑制荷瘤小鼠皮下瘤生长，其纳米载体显示出良好的生物相容性。上述给药系统有望为肿瘤及其他重大疾病联合治疗的药物递送研究提供有益思路。

英文摘要：

In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size （mean diameter of 100.2 ± 15.2 nm）, a homogeneous distribution [the polydispersity index was （0.251 ± 0.018）] and high encapsulation efficiency （90.15 ±2.47） % and （80.64 ± 3.52） % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route.