叶酸脂质体制备工艺优化及其稳定性研究

以叶酸为载药，卵磷脂和胆固醇为膜材，采用薄膜水化- 超声法制备叶酸脂质体；通过单因素考察制备工艺对包封率的影响以及正交设计法进行制备工艺优化。得出最佳制备工艺为卵磷脂与胆固醇比5:1(m/m)、叶酸质量浓度1.4mg/mL、制备温度60℃、水相pH8.0。制备的叶酸脂质体包封率可达到30.36%，平均粒度为335.4nm。将脂质体在4℃下密闭放置15d，以脂质体的粒径变化为指标考察其稳定性。结果表明，脂质体悬液粒径无明显变化，主要集中在300～400nm，脂质体悬液稳定性良好。

Preparation and Stability of Folic Acid Liposomes

The combination of thin film hydration and ultrasonic treatment was used to prepare folic acid liposomes with lecithin and cholesterol as the membrane material and folic acid as the core material. Dialysis-spectrophotometry method was applied to determine the encapsulation efficiency of folic acid liposomes. Based on a series of single-factor experiments, the optimal conditions for preparing folic acid liposomes were explored by orthogonal array design to be preparation temperature of 60 ℃, pH 8.0, the mass ratio between lecithin and cholesterol of 5:1, and folic acid concentration of 1.4 mg/mL. The prepared liposomes under these optimal conditions had an entrapment efficiency of 30.36% with an average particle size of 335.4 nm. The liposomal suspension was sealed in a bottle and stored at 4 ℃ for 15 days for stability evaluation based on measurement of average particle size, and the results indicated that the average particle size had no significant change, which was in the range of 300 to 400 nm, and that the suspension had a good stability.