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Effects of salt addition on the microencapsulation of proteins uisng W/O/W double emulsion technique

机译:W / O / W双乳化技术添加盐对蛋白质微囊化的影响

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摘要

The influence of co-encapsulation of stabiklizing additives together with BSA on microsphere charateristics 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 serun 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 interanl (W_1) aqueous phase,often necessary to stabilize protein or antigen solutions, led to an increase in particle size, particle siae distribution, porosity and specific surface area. Bulk density and encapsulation efficiency decreased. The release profile was characterizsed by a high initial burst due to the highly porous structure. Addition of salt to the external or continuous water phase (W_2),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. Analsis of the specific surface area (BET) showed that the addition of salt to W_2, regardless of the salt concentration in the W_1 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 tow 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 W_2 on microsphere characeteristics 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 protien solution, with high encapsulation efficiency and good microsphere characteristics.
机译:采用改进的水包油包水型乳液溶剂蒸发法(W / O / W),研究了稳定化添加剂与BSA的共包封对微球性能的影响。为此,制备了含有牛血清白蛋白(BSA)的聚(L-丙交酯)微球。相对于共包封的稳定添加剂(如电解质)的影响,分析了载有蛋白的微球的形态,孔隙率,比表面积,粒径,包封效率和药物释放动力学。中间(W_1)水相中的高盐浓度(通常是稳定蛋白质或抗原溶液所必需的)导致粒径,粒径分布,孔隙率和比表面积增加。堆积密度和封装效率降低。由于高度多孔的结构,其释放曲线的特征是高初始突释。但是,将盐添加到外部或连续水相(W_2)中可以稳定封装过程,因此可以改善微球的特性,如致密的形态,减少的初始突释,显着提高的堆积密度和封装效率。比表面积(BET)的分析表明,向W_2添加盐,无论W_1相中的盐浓度如何,都会使微球的表面积减少约23倍。微球的性质受微球形成过程中两个水相和水通量之间渗透压梯度的添加盐的影响。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,通过封装酸性橙63(AO63)研究了低分子量药物和向W_2添加盐的不同时间点对微球特性的影响,证实了BSA所获得的结果。这项研究表明,通过添加盐来修饰外部水相是一种封装稳定的蛋白质溶液的简单有效的方法,具有较高的封装效率和良好的微球特性。

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