Pistel K F, Kissel T
Department of Pharmaceutics and Biopharmacy, Philipps-University, Marburg, Germany.
J Microencapsul. 2000 Jul-Aug;17(4):467-83. doi: 10.1080/026520400405723.
The influence of co-encapsulation of stabilizing additives together with BSA on microsphere characteristics using the modified water-in-oil-in-water emulsion solvent evaporation (W/O/W) method was investigated. For this purpose, poly(L-lactide) microspheres containing bovine serum albumin (BSA) were prepared. The morphology, porosity, specific surface area, particle size, encapsulation efficiency and kinetics of drug release of protein loaded microspheres were analysed in relation to the influence of co-encapsulated stabilizing additives such as electrolytes. High salt concentrations in the internal (W1) aqueous phase, often necessary to stabilize protein or antigen solutions, led to an increase in particle size, particle size distribution, porosity and specific surface area. Bulk density and encapsulation efficiency decreased. The release profile was characterized by a high initial burst due to the highly porous structure. Addition of salt to the external or continuous water phase (W2), however, stabilized the encapsulation process and, therefore, resulted in improved microsphere characteristics as a dense morphology, a reduced initial burst release, a drastically increased bulk density and encapsulation efficiency. Analysis of the specific surface area (BET) showed that the addition of salt to W2, regardless of the salt concentration in the W1 phase, decreased the surface area of the microspheres approximately 23-fold. Microsphere properties were influenced by salts additions through the osmotic pressure gradients between the two aqueous phases and the water flux during microsphere formation. Release profiles and encapsulation efficiencies correlated well with the porosity and the surface area of microspheres. Furthermore, the influence of a low molecular weight drug and different time-points of salt addition to W2 on microsphere characteristics were studied by encapsulation of acid orange 63 (AO63), confirming the results obtained with BSA. This study suggests that modification of the external water phase by adding salts is a simple and efficient method to encapsulate stabilized protein solution, with high encapsulation efficiency and good microsphere characteristics.
研究了使用改进的水包油包水乳液溶剂蒸发（W/O/W）法将稳定添加剂与牛血清白蛋白（BSA）共包封对微球特性的影响。为此，制备了含有牛血清白蛋白（BSA）的聚（L-丙交酯）微球。分析了载蛋白微球的形态、孔隙率、比表面积、粒径、包封效率和药物释放动力学，以研究共包封的稳定添加剂（如电解质）的影响。内部（W1）水相中高盐浓度通常是稳定蛋白质或抗原溶液所必需的，这导致粒径、粒径分布、孔隙率和比表面积增加。堆积密度和包封效率降低。由于高度多孔的结构，释放曲线的特征是具有高初始突释。然而，向外部或连续水相（W2）中添加盐可稳定包封过程，因此，可改善微球特性，使其具有致密的形态、降低的初始突释、显著增加的堆积密度和包封效率。比表面积（BET）分析表明，无论W1相中盐浓度如何，向W2中添加盐都会使微球表面积降低约23倍。微球性质受两水相之间的渗透压梯度和微球形成过程中的水通量影响。释放曲线和包封效率与微球的孔隙率和表面积密切相关。此外，通过包封酸性橙63（AO63）研究了低分子量药物和向W2中添加盐的不同时间点对微球特性的影响，证实了用BSA获得的结果。本研究表明，通过添加盐来修饰外部水相是一种简单有效的方法，可用于包封稳定的蛋白质溶液，具有高包封效率和良好的微球特性。
