载纳豆激酶的三甲基壳聚糖纳米粒的制备及体外释放度研究Δ

摘要

OBJECTIVE:To prepare nattokinase (NK)-loaded trimethyl chitosan (TMC) nanoparticles (TMC-NK-NPs),and to study its release rate in vitro. METHODS:TMC with different degree of quaternization(15%,20%,25%)were synthetized,i.e. TMC15,TMC20,TMC25;those were combined with NK to form TMC-NK-NPs by self-assembly. The particle size,polydispersi-ty index (PDI) and Zeta potential were determined and TCM was screened;the morphology, entrapment efficiency (EE), drug-loading amount,30 d stability at 4 ℃ and dark place,24 h accumulative release rate in vitro (Q) and NK activity of TMC-NK-NPs by optimal formulation were observed and determined. RESULTS:Using TMC20,TMC-NK-NPs were smaller in particle size [(161.0 ± 4.8) nm],the lowest in PDI (0.204);the Zate potential was (19.2 ± 1.5) mV,spherical or spherical-like, EE was(45.4±1.51)%,drug-loading amount was(14.2±0.25)%,stable within 30 d,the peak Q12 h was 92.3%. The maximum released activity of NK was 76.6% at 1 h,but then gradually decreased with time. CONCLUSIONS:TMC-NK-NPs are prepared successfully,round and complete with high EE and drug-loading amount,good sustained-release property.%目的：制备载纳豆激酶（NK）的三甲基壳聚糖（TMC）纳米粒（TMC-NK-NPs），并研究其体外释放度。方法：合成季胺化度分别为15％、20％、25％的TMC（即TMC15、TMC20、TMC25），将其与NK自组装形成TMC-NK-NPs。测定TMC-NK-NPs的粒径、多分散系数（PDI）、Zeta电位，筛选TMC；观察并测定最优处方制备的TMC-NK-NPs的形态、包封率、载药量、4℃避光下30 d的稳定性、24 h内的体外累积释放度（Q）及NK活性。结果：采用TMC20所制TMC-NK-NPs的粒径较小[（161.0±4.8）nm]，PDI最小（0.204），Zeta电位为（19.2±1.5）mV，呈球形或类球形；包封率为（45.4±1.51）％，载药量为（14.2±0.25）％；30 d内相对稳定；峰值Q12 h为92.3％；NK活性在1 h时就达到最大（76.6％），但随着时间延长，活性降低。结论：成功制得形态圆整、包封率与载药量较高，且具有较好缓释作用的TMC-NK-NPs。