盐酸表柔比星长循环热敏脂质体的处方优化及体外释药考察

The Formulation of Epirubicin Hydrochloride Long-Circulating Thermosensitive Liposomes and Drug Release in Vitro

目的制备盐酸表柔比星长循环热敏脂质体(EPI-LTSL)并进行处方优化,考察其体外热敏释药性质。方法pH梯度法制备EPI-LTSL,葡聚糖凝胶法分离脂质体和游离药物以测定包封率,HPLC测定药物含量。进行优化处方,采用荧光淬灭法测定脂质体的体外热敏释药率。结果优选处方制备的EPI-LTSL为半透明橘红色,磷脂质量浓度为75mg.mL-1,二棕榈酰磷脂酰胆碱(DPPC)-肉豆蔻酰溶血磷脂酰胆碱(MSPC)摩尔比为82:8;药脂比为1:10,平均粒径小于100nm,载药量大于2mg.mL-1,包封率99%,相变温度为42.76℃。EPI-LTSL37℃水浴15min的累积释药小于5%,而43℃水浴4min的累积释药达到90%以上。结论制备的EPI-LTSL载药量和包封率较高、粒径较小,热敏释药性质良好。采用荧光淬灭法测定EPI-LTSL体外热敏释药率准确快捷。

OBJECTIVE To prepare epirubicin hydrochloride long-circulating thermosensitive liposomes （EPI-LTSL） and investigate the formulation,to study the characteristics of drug released from LTSL in vitro.METHODS EPI-LTSL were prepared by pH gradients methods,Sephadex G-50 gel filtration method was employed to isolate the liposome and free drug for the entrapment efficiency.HPLC was used to determine drug content.The formulation was polished and the fluorescent quenching method was used to determine the drug content released from LTSL in vitro.RESULTS EPI-LTSL was bright jacinth homogeneous semitransparent colloid solution.The optimized formulations were as follows：the phospholipid concentration was 75 mg·mL-1,DPPC/MSPC was 82：8 （mol/mol）,drug/lipid was 1：10（w/w）,average size was smaller than 100 nm,drug content was greater than 2 mg·mL-1,the entrapment efficiency was 99%,the phase transition temperature was 42.76 ℃.The drug release amount of EPI-LTSL was not more than 5% at 37 ℃ in 15 min,while about 90% of the total drug released at 43 ℃ in 4 min.CONCLUSION The EPI-LTSL showed high drug-loading capability and high encapsulation efficiency,with small sizes and excellent drug release characteristics in vitro.The fluorescent quenching method is simple,rapid and suitable for the determination of EPI released from liposomes.