牛血清白蛋白阳离子微球的制备及体外评价

Preparation and in Vitro Evaluation of Cationic Microspheres Containing Bovine Serum Albumin

关键词:  牛血清白蛋白  壳聚糖  乳酸/羟基乙酸共聚物  微球  体外释放

Key words:  bovine serum albunin  chitosan  PLGA  microsphere  in vitro release

摘要:

目的 制备牛血清白蛋白(BSA)口服阳离子微球，考察天然阳离子物质壳聚糖(CHS)的加入对蛋白微球的粒径、电动电势、包封率、载药量及体外释放情况的影响。方法 以乳酸/羟基乙酸共聚物(PLGA)和壳聚糖(CHS)为载体材料，采用W/O/W复乳-溶剂挥发法制备牛血清白蛋白乳酸/羟基乙酸共聚物-壳聚糖(PLGA/CHS)阳离子微球。通过正交设计优化制备工艺，确定最佳处方。建立准确而简便的蛋白含量测定方法，并对微球进行体外评价。结果 最佳处方为：BSA浓度为150 g·L-1、PLGA浓度为8%、外水相体积为80 mL、壳聚糖浓度为0.2%。制得的微球形态圆整，平均粒径为(6.9±5.5)μm，为表面荷正电的阳离子微球[ζ电势=(10.0±0.6)mV]，包封率为(75.4±4.6)%，载药量为(9.3±0.2)%。体外释放结果表明，在模拟胃液和模拟肠液中，壳聚糖的加入均能减少突释，延缓药物的释放。结论 与PLGA微球相比，制得的PLGA/CHS阳离子微球表面带正电，具有较高的包封率和载药量，可以延缓药物释放，同时减少突释现象。

Abstract:

OBJECTIVE To prepare bovine serum albumin (BSA) cationic microspheres for oral administration, and investigate the influence of natural cationic polysaccharide chitosan (CHS) on size, eletrokinetic potential, encapsulation efficiency, loading capacity and in vitro release profile of BSA microspheres. METHODS PLGA/CHS microspheres were prepared by W/O/W emulsion-solvent evaporation method. Orthogonal design method was used to determine the optimal formulation. A simple and precise method for the determination of the protein content was established. In vitro evaluation of PLGA/CHS microspheres was carried out. RESULTS The optimal formulation was as follows: 150 mg·mL-1 of BSA, 8% PLGA solution, 80 mL of external aqueous phase, 0.2% chitosan solution. The PLGA/CHS microspheres were spherical. The average particle size of the microspheres was (6.9 ± 5.5)μm, the eletrokinetic potential (ζ potential) was (10.0±0.6)mV. The drug loading capacity and encapsulation efficiency were (9.3 ± 0.2)% and (75.4 ± 4.6)%, respectively. In vitro release studies show that chitosan can decrease the burst release and delay the release of drugs in both simulated gastric fluid and simulated intestinal fluid. CONCLUSION Compared with PLGA microspheres, PLGA/CHS cationic microspheres has higher encapsulation efficiency and loading capacity, and slow-release, while reducing burst release.