石杉碱甲脂质体制备及包封率的影响因素

Preparation of huperzine A liposomes and investigation of factors influencing the entrapment efficiencies

目的建立石杉碱甲脂质体(huperzine A liposome,HUPA-L)的制备方法。方法采用pH梯度、硫酸铵[(NH4)2SO4]梯度、乙二胺四乙酸铵(NH4EDTA)梯度方法制备HUPA-L,以阳离子交换树脂分离脂质体和游离药物,HPLC法测定HUPA-L的包封率,并考察温度、孵化时间及药脂比对HUPA-L包封率的影响。体外释放实验研究HUPA-L的释放行为。结果硫酸铵梯度法制备的HU-PA-L包封率最高,包封率随着硫酸铵浓度和温度的升高而增加,随着药脂比的降低而增大,当药物与磷脂质量比小于1∶100时,HUPA-L包封率可达100.0%;HUPA-L体外释放呈现明显的缓释效果。结论硫酸铵梯度法是制备HUPA-L优选方法,硫酸铵的浓度、温度和药脂比是影响包封率的重要因素。

Objective To establish the preparation method of huperzine A liposomes （Huperzine A liposomes, HUPA-L）. Methods HUPA-L was prepared with pH gradient, ammonium sulfate [ （ NH4 ） 2 SO4] gradient and NH4EDTA gradient. A cation exchange resin was used to separate the drug and liposomes ,the entrapment efficiencies of HUPA-L were determined by HPLC, and the factors that influencing the entrapment efficiencies such as temperature, time and drug-to-lipid ratio were investigated. HUPA-L release behavior was studied by in vitro release experiments. Results The highest entrapment efficiency of HUPA-L was obtained by the gradients of ammonium sulfate method, and it increased with the increase of the concentration of the ammonium sulfate and temperature, and the decrease of drug-to-lipid ratio. When drug-to-lipid ratio was less than 1：100 （m： m）, the entrapment efficiency could reach 100%. The in vitro release of HUPA-L showed a significant sustained-release effect. Conclusions The ammonium sulfate gradient method is an optimal method for preparing HUPA-L, and the concentration of ammonium sulfate, temperature and drug-to-lipid ratio are important factors influencing the entrapment efficiencies.