去氢骆驼蓬碱脂质体冻干剂粉的制备工艺优选

Optimization of Preparation Process for Freeze-dried Powder of Harmine Liposome

目的:制备含有不同冻干保护剂的N-三甲基壳聚糖(TMC)包衣去氢骆驼蓬碱脂质体(TMC-HM-LP)的冻干粉,并筛选其最佳制备工艺。方法:用"薄膜分散-pH梯度法"制备去氢骆驼蓬碱脂质体,并采用孵育包衣法、低温高速离心法和结合高效液相色谱(HPLC)定量方法测定其包衣脂质体的包封率;以其冻干粉的外观在冻干前和复溶后脂质体的粒径、包封率作为对比指标,优选出最佳的冻干工艺以及冻干保护剂的种类及比例。结果:以葡萄糖-乳糖-甘露醇(2:1:0.5)作为冻干保护剂,通过"分步预冻"的方法和-80℃冷冻干燥技术得到的TMC-HM-LP外观良好,冻干前后粒径和包封率变化较小。结论:采用冷冻干燥技术并结合冻干保护剂的优选,可显著提高包衣脂质体的稳定性。

Objective:To prepare freeze-dried powder of N-trimethyl chitosan(TMC)-coated harmine liposome(TMC-HM-LP) containing different lyoprotectants for searching the optimization of preparation process.Methods:Harmine liposome was obtained through film dispersion-pH gradient method,and then coated by TMC through incubation.Encapsulation efficiency was measured by high-speed centrifuge method and quantificational technique of high performance liquid chromatography(HPLC).The appearance of freeze-dried powder,particle size and encapsulation efficiency before and after lyophilization were compared so as to optimize the process and lyoprotectants together with their ratios.Results:With an appropriate mass ratio of glucose-lactose-mannitol(2:1:0.5) and by the method of stepped pre-freezing before lyophilization,the obtained lyophilized product was of satisfactory appearance and less difference of particle size and encapsulation efficiency before and after lyophilization.Conclusion:The stability of prepared coated liposome was increased with the aid of adopting lyophilization technique and optimizing the lyoprotectants.