Woo B H, Jiang G, Jo Y W, DeLuca P P
Faculty of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington 40536, USA.
Pharm Res. 2001 Nov;18(11):1600-6. doi: 10.1023/a:1013090700443.
To prepare and characterize a novel composite microsphere system based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(acryloyl hydroxyethyl starch) (acHES) hydrogel for controlled protein delivery.
Model proteins, bovine serum albumin, and horseradish peroxidase were encapsulated in the acHES hydrogel, and then the protein-containing acHES hydrogel particles were fabricated in the PLGA matrix by a solvent extraction or evaporation method. The protein-loaded PLGA-acHES composite microspheres were characterized for protein loading efficiency, particle size, and in vitro protein release. Protein stability was examined by size-exclusion chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and monitoring the enzymatic activity.
Scanning electron microscopy showed discrete PLGA microspheres containing many acHES particles. The composite microspheres were spherical and smooth in size range of 39-93 microm. The drug loading efficiency ranged from 51 to 101%. The composite microspheres showed more favorable in vitro release than conventional PLGA microspheres. The composite microspheres showed 20% less initial with a gradual sustained release compared to high burst (approximately 60%) followed by a very slow release with the conventional PLGA microspheres. The composite microspheres also stabilized encapsulated proteins from the loss of activity during the microsphere preparation and release. Proteins extracted from the composite microspheres showed good stability without protein degradation products and structural integrity changes in the size-exclusion chromatography and SDS-PAGE analyses. Horseradish peroxidase extracted from microspheres retained more than 81% enzymatic activity.
The PLGA-acHES composite microsphere system could be useful for the controlled delivery of protein drugs.
制备并表征一种基于聚（D，L-丙交酯-乙交酯）（PLGA）和聚（丙烯酰羟乙基淀粉）（acHES）水凝胶的新型复合微球系统，用于蛋白质的控释。
将模型蛋白牛血清白蛋白和辣根过氧化物酶包封于acHES水凝胶中，然后通过溶剂萃取或蒸发法在PLGA基质中制备含蛋白的acHES水凝胶颗粒。对载蛋白的PLGA-acHES复合微球进行蛋白载量效率、粒径和体外蛋白释放特性表征。通过尺寸排阻色谱、十二烷基硫酸钠聚丙烯酰胺凝胶电泳（SDS-PAGE）以及监测酶活性来检测蛋白稳定性。
扫描电子显微镜显示离散的PLGA微球中含有许多acHES颗粒。复合微球呈球形且表面光滑，粒径范围为39 - 93微米。载药效率在51%至101%之间。复合微球在体外释放方面比传统PLGA微球更具优势。与传统PLGA微球高突释（约60%）后极缓慢释放相比，复合微球初始突释减少20%，呈现逐渐持续释放。复合微球还能稳定包封的蛋白，使其在微球制备和释放过程中不丧失活性。从复合微球中提取的蛋白在尺寸排阻色谱和SDS-PAGE分析中显示出良好的稳定性，无蛋白降解产物且结构完整性未改变。从微球中提取的辣根过氧化物酶保留了超过81%的酶活性。
PLGA-acHES复合微球系统可用于蛋白质药物的控释。
