Russell-Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Technion City, Haifa 32000, Israel.
Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Technion City, Haifa 32000, Israel.
J Colloid Interface Sci. 2015 Jul 1;449:514-21. doi: 10.1016/j.jcis.2015.02.030. Epub 2015 Feb 18.
β-Casein is a 24 kDa amphiphilic and unstructured protein that self-assembles into small core-shell micelles at a wide range of concentrations, pH values and temperatures. We recently developed the micelles as nanocarriers for oral delivery of hydrophobic drugs. In this paper we examined the effect of the hydrophobic non-steroidal anti-inflammatory drug (NSAID) ibuprofen on the micellar structure, as a function of temperature and loading. Using cryo-transmission electron microscopy (cryo-TEM) we find two routes of organization – mixed micellization and co-assembly (aggregation). The time-dependent events that characterize the second routes has been examined in detail. At 25 °C we find coexistence of small assemblies and larger aggregates of irregular (but defined) structures that contain the drug. Increasing the drug loading increases the relative number of the larger aggregates and their dimensions, leading eventually to the formation of long then branched structures, like in amphiphilic block copolymer solutions. Similar trends were identified for changes in the temperature. Combined, our results suggest that ibuprofen acts as a co-surfactant that possibly is localizes to the interface rather than being encapsulated in the micellar core as other NSAID hydrophobic drugs.
β-酪蛋白是一种 24kDa 的两亲性无定形蛋白质，可在广泛的浓度、pH 值和温度范围内自组装成小型核壳型胶束。我们最近将这些胶束开发为用于口服递送疏水性药物的纳米载体。在本文中，我们研究了疏水性非甾体抗炎药（NSAID）布洛芬对胶束结构的影响，这是温度和负载的函数。使用低温透射电子显微镜（cryo-TEM），我们发现了两种组织方式 - 混合胶束化和共组装（聚集）。详细研究了表征第二种途径的时变事件。在 25°C 下，我们发现小组装体和较大的不规则（但定义明确）结构的聚集体共存，其中包含药物。增加药物负载量会增加较大聚集体的相对数量及其尺寸，最终导致形成长而分支的结构，类似于两亲嵌段共聚物溶液。温度变化也出现了类似的趋势。综合来看，我们的结果表明，布洛芬作为一种助表面活性剂，可能定位于界面而不是被其他 NSAID 疏水性药物包裹在胶束核中。
