甘草次酸-长循环阿霉素脂质体的制备及其靶向性研究

Glycyrrhetinic acid-long circulation adriamycin loaded liposomes:preparation and in vivo targeting study

目的合成甘草次酸(GA)修饰的聚乙二醇(PEG)-磷脂衍生物,制备甘草次酸-长循环阿霉素脂质体(GA-PLIP@ADM),研究其体外制剂学相关性质和小鼠体内靶向性。方法合成GA修饰的PEG-DSPE,差示扫描量热法、核磁共振氢谱和飞行质谱法表征合成产物;采用薄膜分散法制备GA-PLIP@ADM,并测定其包封率和载药量;动态光散射法测定其粒径和zeta电位,透射电镜观察外观形态;考察其稳定性;建立阿霉素体内分析方法,研究GA-PLIP@ADM的体内靶向性。结果采用合成GA修饰的PEG-磷脂衍生物制备的GA-PLIP@ADM包封率和载药量分别为(60.6±4.5)%和(4.22±0.32)%,平均粒径为(127.2±5.2)nm;外观为球形或类球形,大小均一;稳定性良好;小鼠体内靶向性研究结果表明,GA-PLIP@ADM具有明显的肝脏和肿瘤靶向性。结论甘草次酸-长循环阿霉素脂质体作为肝脏靶向和肿瘤靶向给药系统,具有广阔的应用前景。

Objective To synthesize glycyrrhetinic acid(GA)modified polyethylene glycol(PEG)-phospholipid derivative and prepare glycyrrhetinic acid-long circulating adriamycin loaded liposomes(GA-PLIP@ADM),and to study its related properties in vitro and targeting study in vivo.Methods GA-PEG-phospholipid derivatives were synthesized and characterized by DSC,~1H-NMR and MALDI-TOF-MS.GA-PLIP@ADM was prepared by thin film dispersion method.The encapsulation efficiency and drug loading were determined by cation exchange resin method.Its particle size and zeta potential were determined by dynamic light scattering method,and its morphology was observed by TEM.Fluorescence spectrophotometry was used to study the in vivo targeting ability of GA-PLIP@ADM.Results The encapsulation efficiency and drug loading of GA-PLIP@ADM prepared by synthetic GA-PEG-phospholipid derivatives were(60.6±4.5)%and(4.22±0.32)%,respectively.The average particle size was(127.2±5.2)nm.The appearance of GA-PLIP@ADM was spherical or almost spherical,and the size was uniform.GA-PLIP@ADM possessed obvious liver and tumor targeting properties in vivo.Conclusion GA-PLIP@ADM is a promising drug delivery system for liver targeting and tumor targeting.