羟基喜树碱包衣纳米脂质体的处方及制备工艺研究

Study on formulation and preparation of chitosan chloride coated hydroxycamptothecin nanoliposomes

目的研究羟基喜树碱包衣纳米脂质体的处方筛选及制备工艺。方法采用薄膜分散法制备羟基喜树碱脂质体;用柱色谱法分离游离药物;用紫外分光光度法测定包封率;用正交实验优选处方;用氯化壳聚糖包被脂质体,经高压乳匀得到纳米脂质体(<100nm)并测定Zeta电位、粒径大小及分布;用不同冻干保护剂进行冷冻干燥,以筛选合适的保护剂。结果最佳处方制备的药物平均包封率为(68.8±0.9)%(n=3);包衣纳米脂质体的Zeta电位为55.1mV,平均粒径为90.9nm,粒径分布为20-120nm;以15%海藻糖做冻干保护剂的脂质体冻干前后粒径变化最小。结论本试验制备的羟基喜树碱包衣纳米脂质体具有包封率高,稳定性好,表面带正电荷等特点,为其进一步研究奠定了基础。

OBJECTIVE: To screen the optimal formulation and preparation of the coated hydroxycamptothecin(HCPT)nanoliposomes(N-liposomes). METHODS: HCPT liposomes were prepared by the film dispersion method. Liposomes and unloaded HCPT were separated by Sephadex - G50 chromatography. Ultraviolet spectrophotometry was used to determine the entrapment efficiency of HCPT N-liposomes. Orthogonal design was used to select the optimum formulation. Chitosan chloride (CS-Cl )was used to coat the liposomes, then the liposomes were extruded through high pressure homogenizer. Zetasizer was used to determine the zeta potential, average size and size distribution of the HCPT Liposomes. Different cryoprotectants were used during lyophilization in order to select the best one. RESULTS: The average entrapment efficiency of the optimal formulation was (68.8 ± 0.9)%(n = 3). The Zeta potential of the CS-Cl coated HCPT N-liposomes was 55.1 mV and the average size was 90.9 nm with the size distribution of 20-120 run. The particle size was changed least after lyophilization when 15% trehalose was used as cryoprotectant. CONCLUSION: The formulation and preparation process were practical to prepare the CS-Cl coated HCPT N-liposomes with promising entrapment efficiency and stability. It was valuable to be further studied.