重酒石酸长春瑞滨热敏脂质体的制备及其包封率测定方法研究

 目的 制备重酒石酸长春瑞滨（vinorelbine tartrate, VRT）热敏脂质体,建立脂质体中VRT含量和包封率的测定方法。方法 pH梯度法制备VRT热敏脂质体,HPLC测定脂质体中VRT的含量。微柱离心法分离脂质体与游离药,考察葡聚糖凝胶类型、洗脱溶剂、柱高、洗脱体积等因素对VRT游离药洗脱的影响。结果 VRT热敏脂质体的平均粒径为（94.6±1.6）nm,含量为（1.83±0.03）mg·mL-1。选择葡聚糖凝胶G-25制备微柱,最佳柱高4 cm,以PBS缓冲液为洗脱溶剂,梯度洗脱体积法分离脂质体与游离药,测得3批VRT热敏脂质体的包封率分别为（95.75±1.42）%、（91.12±1.21）%、（94.10±2.03）%,洗脱回收率分别为（98.3±2.42）%、（93.5±1.83）%、（96.6±1.65）%。结论 VRT脂质体的制备工艺稳定,载药量大,包封率高。含量及其包封率测定方法简单、快速、准确。本实验可为VRT静脉注射用热敏脂质体新制剂的开发提供研究基础。

Preparation and Entrapment Efficiency of Vinorelbine Tartrate Thermo-sensitive Liposomes

OBJECTIVE To prepare vinorelbine tartrate（VRT） thermo-sensitive liposomes and establish methods for determining its VRT content and entrapment efficiency. METHODS VRT thermo-sensitive liposomes were prepared by pH-gradients method. VRT contents were determined by HPLC. Liposomes and free drug were separated by mini-column centrifugation. The influential factors of VRT elution including sephadex type, elution solution, and column height and elution volume were investigated. RESULTS Mean particle size of VRT thermo-sensitive liposomes was （94.6±1.6）nm. VRT content was （1.83±0.03） mg·mL^-1. The entrapment efficiencies of three batches of VRT thermo-sensitive liposomes were （95.75±1.42）%, （91.12±1.21）% and （94.10±2.03）%, and the elution recoveries were （98.3±2.42）%, （93.5±1.83）% and （96.6±1.65）%. Sephadex G-25 was chosen to prepare mini-column. Elution solution were PBS, 4 cm of column height was optimal, and one of gradients-elution-volumes was ascertained. CONCLUSION The preparation technology of VRT liposomes was stable, drug loading and entrapping capacity of VRT liposomes were well. The methods for determination of VRT content and entrapment efficiency were simple, rapid and accurate. These studies can provide bases for further development of intravenous injection VRT thermo-sensitive liposomes.