目的 制備性質穩(wěn)定的硫酸長春新堿脂質體。方法 采用單因素試驗考察磷脂與膽固醇比例、藥脂比、脂質濃度、載藥溫度、載藥時間、外水相pH值對硫酸長春新堿脂質體包封率的影響。以包封率為指標, 分別以氫化磷脂(SPC-3)和二硬脂酰磷脂酰膽堿(DSPC)為磷脂材料, 通過正交試驗考察載藥溫度、藥脂比和載藥時間對制備工藝的影響, 優(yōu)化出硫酸長春新堿脂質體的最佳制備工藝。結果 硫酸長春新堿脂質體的最佳制備工藝為:將藥物溶液(按照藥物含量計)和空白脂質體溶液(按照脂質含量計)按照1:20的比例混合, 用Na₂HPO₄直接調節(jié)外水相pH值至7.2。SPC-3脂質體在65 ℃條件下載藥, 載藥時間30 min。DSPC脂質體在60 ℃條件下載藥, 載藥時間10 min。結論 優(yōu)選出的硫酸長春新堿脂質體的處方工藝穩(wěn)定可行。

Objective To prepare stable Vincristine Sulfate Liposomes. Methods Single factor tests were used to investigate the effects of formulation and process factors, such as phospholipids and cholesterol radio, drug fat ratio, fat concentration, drug loading temperature, drug loading time, and pH value of water external phase on the encapsulation efficiency of Vincristine Sulfate Liposomes. Then, the optimal preparation technology of Vincristine Sulfate Liposomes with SPC-3 and DSPC as phospholipid material was optimized by orthogonal test to investigate influence of drug loading temperature, drug fat ratio, and drug loading time to the preparation technology, taking encapsulation efficiency as index. Results The best formulation and process of Vincristine Sulfate Liposomes was as following: vincristine sulfate solution and blank liposome solution was mixed by the ratio of 1:20, and then Na₂HPO₄ was used to regulate the pH value of liposome external phase to 7.2. SPC-3 liposomes uptook drugs at 65 ℃, and the drug loading time was 30 min. DSPC liposomes uptook drugs at 60 ℃, and the drug loading time was 10 min. Conclusion The optimized preparation technology of Vincristine Sulfate Liposomes is stable and feasible.

國家重大新藥創(chuàng)制項目(2014ZX09507005-001)