CAJ | 학술논문

目的构建长春新碱抗耐药性隐形脂质体,并考察其在大鼠体内的药动学.方法采用硫酸铵梯度法制备长春新碱抗耐药性隐形脂质体;将Spmgue桪awley大鼠分成两组,分别尾静脉注射长春新碱抗耐药性隐形脂质体和游离药,用高效液相二极管阵列色谱法和高效液相荧光色谱法分别测定血浆中长春新碱和奎纳克林的浓度,通过与游离药组比较,评价长春新碱抗耐药性隐形脂质组的药动学特点.结果长春新碱抗耐药性隐形脂质体的粒径为135.9±7.1nm,其中,长春新碱的包封率大于90%,奎纳克林的包封率大于85%;大鼠尾静脉注射长春新碱抗耐药性隐形脂质体后,与游离药组相比,长春新碱和奎纳克林的血液滞留时间明显增长,并且两者平均血药浓度都明显提高.在长春新碱抗耐药性隐形脂质体组中,长春新碱和奎纳克林的Cmax,t1/2和AUC0-24 h都分别高于游离药组的相应值,然而,长春新碱和奎纳克林的C1都明显低于游离药组的值.结论本研究成功构建了具有高包封率的长春新碱抗耐药性隐形脂质体.抗耐药性隐形脂质体明显延了长春新碱和奎纳克林在血液中的循环时间并提高了二者血浆中平均血药浓度.
목적 구건장춘신감항내약성은형지질체,병고찰기재대서체내적약동학.방법 채용류산안제도법제비장춘신감항내약성은형지질체;장Spmgue심awley대서분성량조,분별미정맥주사장춘신감항내약성은형지질체화유리약,용고효액상이겁관진렬색보법화고효액상형광색보법분별측정혈장중장춘신감화규납극림적농도,통과여유리약조비교,평개장춘신감항내약성은형지질조적약동학특점.결과 장춘신감항내약성은형지질체적립경위135.9±7.1nm,기중,장춘신감적포봉솔대우90%,규납극림적포봉솔대우85%;대서미정맥주사장춘신감항내약성은형지질체후,여유리약조상비,장춘신감화규납극림적혈액체류시간명현증장,병차량자평균혈약농도도명현제고.재장춘신감항내약성은형지질체조중,장춘신감화규납극림적Cmax,t1/2화AUC0-24 h도분별고우유리약조적상응치,연이,장춘신감화규납극림적C1도명현저우유리약조적치.결론 본연구성공구건료구유고포봉솔적장춘신감항내약성은형지질체.항내약성은형지질체명현연료장춘신감화규납극림재혈액중적순배시간병제고료이자혈장중평균혈약농도.
Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared by incorporating vincristine with quinacrine together using the ammonium sulfate gradient loading procedure. For the pharrnacokinetic study, Sprague-Dawley rats were divided into two groups: each rat in the Group I was administered intravenously via tail vein as stealthy liposomal vincristine plus quinacrine, and the Group Ⅱ similarly given as a mixture solution of free vincristine plus free quinacrine. The concentrations of vincristine and quinacrine in plasma were measured by HPLC with diode array detection and fluorescence detection, respectively. Results The mean particle size of stealthy liposomes was 135.9±7.1 nm and the encapsulation efficiencies of stealthy liposomes were＞90% for vincristine, and＞85% for quinacrine, respectively. Administered as the stealthy vincristine plus quinacrine liposomes, the plasma exposures of both vincristine and quinacrine were significantly extended, and the mean concentrations of both vincristine and quinacrine were significantly higher compared to those given as the mixture solution of free vincristine plus free quinacrine. The C,max,t1/2 AUC0-24 h values of vincristine for stealthy liposomal group were significantly increased, but the total clearance C1 values decreased, as compared to those of free drug group, respectively. Similarly, the Cmax,t1/2 and AUC0-24 h values of quinacrine for the stealthy liposomal group were significantly increased, but the total clearance C1 values decreased, as compared to those of free quinacrine. Conclusion The anti-resistant stealthy liposomes are successfully prepared by incorporating vincristine with quinacrine, and the liposomes extend significantly the duration in blood circulation and improve evidently the plasma concentrations of both vincristine and quinacrine.