CAJ | 학술논문

构建依托泊苷隐形前体脂质体,并考察其在家兔体内的药动学.采用薄膜分散法构建卒白隐形脂质体;硫酸铵梯度法包封依托泊苷;结合真空冷冻干燥技术构建依托泊苷隐形前体脂质体.采用凝胶色谱法测定脂质体包封率;透射电镜观察脂质体的形态;电泳光散射技术测定Zeta电位与粒径分布;以市售依托泊苷注射液和普通脂质体为参比制剂,评价其在家兔体内药动学特点.脂质体平均包封率为83.92%±3.65%,粒径为(124.5±26.9)nm,Zeta电位为(-39.50±1.04)mV,家兔单剂量静脉注射1.5 me/kg依托泊苷制剂后呈二室模型特征,依托泊苷隐形前体脂质体的T1/2β为(19.26±3.16)h,AUC为(26.04 ±3.53)μg/h/mL;注射液的T1/2β为(0.94±0.21)h,AUC为(0.98 ±0.26)μg/h/mL;普通脂质体的T1/2β为(7.99±1.36)h,AUC为(11.65±1.70)μg/h/mL.构建的隐形前体脂质体包封率高,且延长了依托泊苷在血液中的循环时间.
구건의탁박감은형전체지질체,병고찰기재가토체내적약동학.채용박막분산법구건졸백은형지질체;류산안제도법포봉의탁박감;결합진공냉동간조기술구건의탁박감은형전체지질체.채용응효색보법측정지질체포봉솔;투사전경관찰지질체적형태;전영광산사기술측정Zeta전위여립경분포;이시수의탁박감주사액화보통지질체위삼비제제,평개기재가토체내약동학특점.지질체평균포봉솔위83.92%±3.65%,립경위(124.5±26.9)nm,Zeta전위위(-39.50±1.04)mV,가토단제량정맥주사1.5 me/kg의탁박감제제후정이실모형특정,의탁박감은형전체지질체적T1/2β위(19.26±3.16)h,AUC위(26.04 ±3.53)μg/h/mL;주사액적T1/2β위(0.94±0.21)h,AUC위(0.98 ±0.26)μg/h/mL;보통지질체적T1/2β위(7.99±1.36)h,AUC위(11.65±1.70)μg/h/mL.구건적은형전체지질체포봉솔고,차연장료의탁박감재혈액중적순배시간.
The objectives of the present study were to prepare stealthy etoposide proliposomes and study the pharmacokinetics in rabbits.Blank stealthy liposomes were prepared by film dispersion method.Stealthy etoposide liposomes were prepared by using the ammonium sulfate gradient loading procedure.Vacuum freeze-drying technique was used to dry stealthy etoposide liposomes.Encapsulation efficiency of stealthy etoposide proliposomes was determined by Sephadex chromatography.The morphology was observed by transmission electronic microscope.The particle size and zeta potential were measured by using electrophoretic light scattering technology.The pharmacokinetics in rabbits was evaluated by comparison with etoposide injection and conventional iiposomes,respectively.Mean encapsulation efficiency of stealthy etoposide proliposomes was 83.92% ± 3.65% (n = 3).The liposomes were round or oval.Mean particle size was (124.5 ± 26.9) nm,and zeta potential was (-39.50 ± 1.04) mV.Following intravenous injection administration at a dose of 1.5 mg/kg etoposide,the three kinds of etoposide preparations were fitted with the two-compartment model.T1/2β and AUC values of stealthy etoposide proliposomes were (19.26 ± 3.16) h and (26.04 ± 3.53) μg/h/mL,respectively.T1/2β and AUC values of etoposide injection were (0.94 ± 0.21) h and (0.98 4- 0.26) μg/h/mL,respectively.T1/2β and AUC values of conventional liposomes were (7.99 ± 1.36) h and (11.65 ± 1.70) μg/h/mL,respectively.Results indicated that the stealthy etoposide proliposomes could significantly extend the duration of etoposide in blood circulation.