Eshel-Green Tal, Bianco-Peled Havazelet
The Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 32000, Israel.
The Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 32000, Israel; Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Colloids Surf B Biointerfaces. 2016 Mar 1;139:42-51. doi: 10.1016/j.colsurfb.2015.11.044. Epub 2015 Dec 2.
Blockpolymer micelles having acrylated end groups were fabricated for the development of mucoadhesive drug loaded vehicle. The critical micelle concentration (CMC) of Pluronic(®) F127 modified with acrylate end groups (F127DA) was found to be similar to that of the unmodified Pluronic(®) F127 (F127). Small angle X-ray scattering verified existence of micelles with an inner core of 4.9±0.2 and 5.5±0.3 for F127 and F127DA respectively. Indomethacin, a hydrophobic drug, was incorporated into the micelles using the thin-film hydration method. In vitro drug release assay demonstrated that the micelles sustained the release of the drug in comparison with free drug in solution. Several methods were used for mucoadhesion evaluation. Viscosity profiling was performed by shear rate sweep experiment of hydrated commercial mucin, F127 or F127DA, and combination of both mucin and a copolymer. Elevated viscosity was achieved for acrylated micelles with mucin compared to mixtures of non-acrylated micelles with mucin. The mucoadhesivity of the acrylated micelles was further characterized using nuclear magnetic resonance (NMR); data affirmed the Michael type addition reaction occurred between acrylates on the micelles corona and thiols present in the mucin. SAXS scattering data further showed a modification in the scattering of F127DA micelles with the addition of pig gastric mucin. Cryo-transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) data detected increase in the aggregates size while using acrylated micelles enhance mucoadhesion. Thus acrylated F127DA micelles were found to be mucoadhesive, and a suitable and preferred candidate for micellar drug delivery to mucosal surfaces.
为了开发载有药物的粘膜粘附载体，制备了具有丙烯酸化端基的嵌段聚合物胶束。发现用丙烯酸酯端基改性的普朗尼克（®）F127（F127DA）的临界胶束浓度（CMC）与未改性的普朗尼克（®）F127（F127）相似。小角X射线散射证实了分别存在F127和F127DA的胶束，其内核分别为4.9±0.2和5.5±0.3。采用薄膜水化法将疏水性药物吲哚美辛包封于胶束中。体外药物释放试验表明，与溶液中的游离药物相比，胶束可持续释放药物。采用多种方法进行粘膜粘附性评价。通过对水合商业粘蛋白、F127或F127DA以及粘蛋白与共聚物的组合进行剪切速率扫描实验来进行粘度分析。与未丙烯酸化的胶束与粘蛋白的混合物相比，丙烯酸化胶束与粘蛋白的混合物粘度升高。使用核磁共振（NMR）进一步表征了丙烯酸化胶束的粘膜粘附性；数据证实了胶束冠上的丙烯酸酯与粘蛋白中存在的硫醇之间发生了迈克尔型加成反应。SAXS散射数据进一步表明，添加猪胃粘蛋白后，F127DA胶束的散射发生了变化。冷冻透射电子显微镜（cryo-TEM）和动态光散射（DLS）数据检测到，使用丙烯酸化胶束增强粘膜粘附性时，聚集体尺寸增加。因此，发现丙烯酸化的F127DA胶束具有粘膜粘附性，是用于粘膜表面胶束药物递送的合适且优选的候选物。
