Elversson Jessica, Millqvist-Fureby Anna
YKI, Institute for Surface Chemistry, Box 5607, 11486 Stockholm, Sweden.
Int J Pharm. 2005 Apr 27;294(1-2):73-87. doi: 10.1016/j.ijpharm.2005.01.015.
This study investigates to what extent an aqueous two-phase system (ATPS) can encapsulate and protect the secondary structure of a protein during spray drying. The ATPSs contained polyvinyl alcohol (PVA) and dextran solutions, in different proportions. A model protein, bovine serum albumin (BSA) and, in some experiments, trehalose were added to the ATPS prior to spray drying. Electron spectroscopy for chemical analysis (ESCA), differential scanning calorimetry (DSC), UV spectrophotometry, size exclusion high-performance liquid chromatography (SEC-HPLC) and Fourier transform infrared spectroscopy (FTIR) were used for analysis of solid and reconstituted samples. The anticipated function of the ATPS was to improve the stability of the protein by preventing interactions with the air-liquid interface during drying and by improving the encapsulation of the protein in the dried powder. BSA was found to preferentially partition to the dextran phase and in the absence of PVA, BSA dominated the powder surface. In samples containing PVA, the polymer mainly covered the powder surface, even though the dextran-rich phase was continuous, thus preventing protein surface interactions and providing improved encapsulation. However, PVA was found to cause partial loss of the native structure of BSA although the protein was well encapsulated during spray drying.
本研究调查了双水相系统（ATPS）在喷雾干燥过程中能够在多大程度上包裹和保护蛋白质的二级结构。这些双水相系统含有不同比例的聚乙烯醇（PVA）和葡聚糖溶液。在喷雾干燥之前，将一种模型蛋白质牛血清白蛋白（BSA）以及在某些实验中加入海藻糖添加到双水相系统中。采用化学分析电子能谱（ESCA）、差示扫描量热法（DSC）、紫外分光光度法、尺寸排阻高效液相色谱法（SEC-HPLC）和傅里叶变换红外光谱法（FTIR）对固体和复溶样品进行分析。双水相系统的预期功能是通过在干燥过程中防止蛋白质与气液界面相互作用以及通过改善蛋白质在干粉中的包裹来提高蛋白质的稳定性。发现BSA优先分配到葡聚糖相，并且在没有PVA的情况下，BSA在粉末表面占主导地位。在含有PVA的样品中，尽管富含葡聚糖的相是连续的，但聚合物主要覆盖在粉末表面，从而防止蛋白质表面相互作用并提供更好的包裹。然而，发现PVA会导致BSA天然结构的部分丧失，尽管蛋白质在喷雾干燥过程中被良好地包裹。
