N-三甲基壳聚糖包衣的盐酸阿霉素脂质体的制备

Preparation of Adriamycin Liposomes Coated by N-trimethyl Chitosan

目的:研制N-三甲基壳聚糖(TMC)包衣的盐酸阿霉素(ADM)脂质体。方法:采用硫酸铵梯度法制备ADM脂质体,以包封率为指标,筛选盐酸阿霉素脂质体最佳处方;合成不同季铵化程度的TMC,并对最佳ADM脂质体进行包衣。结果:未包衣ADM脂质体平均粒径为(378.6±5.2)nm,Zeta电位为(-62.08±2.5)mv,平均包封率为(62.27±1.75)%(n=3)。TMC包衣后,脂质体粒径增大,并随着TMC季铵化程度的增大,Zeta电位显著增大(P<0.05);TMC20、TMC40、TMC60包衣脂质体体外释药曲线符合Higuchi方程,分别为:Q=7.6315+3.7863t_(1/2)(r=0.929 2),Q=6.9647+3.5709t_(1/2)(r=0.9318),Q= 7.3451+2.7665t_(1/2)(r=0.935 7)。结论:TMC包衣ADM脂质体的制备工艺可行,其表面带有较高正电性,为下一步研究其血管靶向性打下基础。

To prepare adriamycin （ADM） liposomes coated by N-trimethyl chitosan （TMC）. Method： Ammonium sulphate gradient method was used for preparation of ADM liposomes and entrapment efficiency was the index to screen the optimal prescription of ADM liposomes. The TMC with different degree of quarternization （DQ） were synthesed followed by the optimal prescription of ADM liposomes was coated. Result： Mean diameter of ADM liposomes before coated was 378.6nm ± 5.2nm, the zeta potential was （ - 62.08 ± 2.5 ） mv and mean entrapment efficiency was （ 62.27 ± 1.75 ） % （ n = 3 ）. The particle size of ADM liposomes was increased after coated by TMC. As the increase of DQ of TMC, the zeta potential of TMC-coated ADM liposomes was increased remarkably （P 〈 0.05 ）. The release of TMC20 ,TMC40 and TMC60-coated ADM liposomes in vitro were accorded with the Higuehi equation, respectively： Q = 7.6315 ＋ 3. 7863t11/2 （ r = 0. 929 2 ）, Q = 6. 9647 ＋ 3. 5709t1/2 （ r = 0.931 8 ）, Q = 7.3451 ＋ 2.7665t1/2 （ r = 0. 935 7 ）. Conclusion： The preparation of ADM liposomes coated by different DQ of TMC is feasible. Their positive zeta potential is the basis of the luther study on tumor neovasculature target.