紫杉醇棕榈酸酯的合成及其脂质体的制备与处方研究  

Synthesis of paclitaxel palmitate and the formulation optimization of its liposomes

作　　者：陈炳辰 王思真 郭贝贝 杨峰 CHEN Bingchen;WANG Sizhen;GUO Beibei;YANG Feng(Department of Colorectal Surgery,The First Affiliated Hospital,School of Pharmacy,Naval Medical University,Shanghai 200433,China;Department of Inorganic Chemistry,School of Pharmacy,Naval Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学第一附属医院肛肠外科,上海200433 [2]海军军医大学药学系无机化学教研室,上海200433

出　　处：《药学实践与服务》2024年第9期379-384,410,共7页Journal of Pharmaceutical Practice and Service

基　　金：国家自然科学基金(82304455);海军军医大学校级课题(2023MS009)。

摘　　要：目的通过对紫杉醇(PTX)的结构改造联合相应脂质体的构建,改善肿瘤细胞摄取,增加药物疗效。方法通过酯化反应制备了紫杉醇前药PTX-PA,并建立含量方法学研究。采用单因素筛选,结合粒径、包封率等指标评价不同方法、条件下制备的PTX-PA/Lip,确定其最佳处方和制备工艺。结果通过酯化反应成功制备PTX-PA,且建立的HPLC定量分析方法符合方法学要求。利用单因素筛选,确定了PTX-PA/Lip的最佳处方和制备工艺,通过最优处方制备的PTX-PA/Lip纳米粒径为(2.75±1.81)nm,PDI为(0.076±0.020),药物包封率达到90%以上。结论基于纳米技术成功制备出棕榈酸修饰的紫杉醇脂质体,增强了紫杉醇在靶细胞的递送,为PTX-PA的药效学研究奠定基础。Objective To improve the cellular uptake efficiency and the therapeutic effect through the structural modification of paclitaxel(PTX)and the preparation of corresponding liposomes.Methods The prodrug of paclitaxel,PTX-PA,was prepared by esterification reaction,and the quantitative detection method of PTX-PA was established.Next,the optimal formulation and preparation of PTX-PA/Lip was obtained through single factor screening based on their appearance,particle size,and encapsulation efficiency.Results The PTX-PA was successfully synthesized,and the established HPLC quantitative analysis method for PTX-PA met the methodological requirements.After the optimal preparation and formulation research through single factor screening,the particle size of optimized PTX-PA/Lip was(62.75±1.81)nm with a PDI of(0.076±0.02),while the drug encapsulation rate reached more than 90%.Conclusion This research successfully prepared palmitic acid modified paclitaxel liposomes based on nanotechnology,enhancing the drug delivery efficiency of paclitaxel and laying the foundation for the pharmacodynamics research of PTX-PA.

关 键 词：紫杉醇 棕榈酸 脂质体 前药 制剂学研究 

分 类 号：R943[医药卫生—药剂学] TQ460.4[医药卫生—药学]