多层海藻酸-壳聚糖聚电解质膜微球的制备与体外释放特性研究

目的：制备牛血清白蛋白-海藻酸-壳聚糖微球（BSA-ACM）,牛血清白蛋白-海藻酸-壳聚糖-海藻酸钠微球（BSA-ACAM）,牛血清白蛋白-海藻酸-壳聚糖-海藻酸-壳聚糖-海藻酸钠微球（BSA-ACACAM）。方法：以海藻酸钠和壳聚糖溶液为囊材,对BSA进行反复包裹,采用乳化-交联法制备BSA-ACM、BSA-ACAM、BSA-ACACAM;采用扫描电镜测定微球粒径,Micro-BCA试剂盒测定载药量,考察包封率和24h体外释药特性,并进行Higuchi方程拟合。结果：BSA-ACM、BSA-ACAM、BSA-ACACAM微球球形圆整,分散性好,平均粒径分别为（3.79±1.33）、（3.52±0.96）、（3.07±1.17）μm;载药量分别为（17.97±1.33）%、（16.95±0.46）%、（16.47±1.49）%;包封率分别为（65.78±4.98）%、（63.99±4.83）%、（55.00±1.50）%。微球体外释放速率与聚电解质膜包裹层数呈负相关,均符合Higuchi方程（r分别为0.9787、0.9869、0.9808）,24h内累积释放量分别为32.15%、25.59%、16.72%,无明显突释现象。结论：多层海藻酸-壳聚糖聚电解质膜微球能减少药物的突释,具有良好的缓释效果。

Preparation and in vitro Release Study of Multilayer-sodium Alginatechitosan Microspheres with Polyelectrolytes Film

OBJECTIVE： To prepare Bovine serum albumin-alginic acid-chitosan microspheres （BSA-ACM）, BSA-alginic acid-chitosan-sodium alginate microspheres （BSA-ACAM） and BSA-alginic acid-chitosan-alginic acid-chitosan-sodium alginate microspheres （BSA-ACACAM）. METHODS： With sodium alginate and chitosan as package material, BSA was packaged repeatedly and then BSA-ACM, BSA-ACAM and BSA-ACACAM were prepared with emulsion-crosslinking method. SEM was utilized to investigate the particle size of the microspheres, the drug-loading amount was detected by Micro-BCA kit, and entrapment efficiency and 24 h release behavior in vitro were also studied. The fitting of Higuchi equation was carried out. RESULTS： BSA-ACM, BSAACAM and BSA-ACACAM were spherical in shape and good in dispersibility. The mean diameters were （3.79 ± 1.33） μm, （3.52 ± 0.96） μm and （3.07 ± 1.17） μm respectively. The drug-loading amount were （17.97 ± 1.33）%, （16.95± 0.46）% and （16.47 ± 1.49） % ; entrapment efficiency were （65.78 ± 4.98）%, （63.99± 4.83）% and （55.00 ± 1.50） %, respectively, Release rate was negatively correlated with the number of polyelectrolytes film layer, which were in line with Higuchi equation. The value of r were 0.978 7, 0.986 9 and 0.980 8, and 24 h accumulative release amounts were 32.15%, 25.59% and 16.72%. No significant burst release was found. CONCLUSIONS ： The burst release of multilayer-sodium alginate-chitosan microspheres with polyelectrolytes film can be decreased, showing sound sustained-release effect.