Laboratory of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Gerhard-Domagk-Str. 3, D-53121 Bonn, Germany.
Laboratory of Pharmaceutical Engineering, University of Franche-Comté, Besançon, France.
J Control Release. 2013 Nov 28;172(1):62-68. doi: 10.1016/j.jconrel.2013.07.031. Epub 2013 Aug 9.
Inflammatory bowel disease is a chronic relapsing inflammation of the gut with the two main forms being ulcerative colitis and Crohn's disease. Nanoparticulate drug carrier systems have been proven to enhance the therapeutic efficiency and to diminish adverse effects of the anti-inflammatory treatment due to their size dependent accumulation in the inflamed regions of the gut. The influence of surface properties on the accumulation selectivity and intensity of such nanoparticles is mainly unclear. Accordingly sized particles (~200 nm) were prepared by the emulsification solvent evaporation technique using different surfactants (polysorbate 20, sodium dodecyl sulphate, sodium cholate, cetyltrimethylammonium bromide, polyvinyl alcohol). In a murine colitis model the particles prepared with polysorbate 20 as surfactant led to a 34.8-fold higher particle content in the inflamed areas of the colon compared to the healthy gut and to a 4.5-fold increase of the particle content in the inflamed segments compared to particles prepared with sodium dodecyl sulphate. This effect translates also into a significantly higher mitigating effect when entrapping betamethasone into such nanoparticles. This study shows the importance of surface properties for the passive targeting approach in experimental colitis. The influence seems to be as important as the influence of the particle size.
炎症性肠病是一种慢性复发性肠道炎症,主要有两种形式:溃疡性结肠炎和克罗恩病。纳米颗粒药物载体系统已被证明可以提高治疗效率,并减少抗炎治疗的不良反应,因为它们的大小依赖于在肠道炎症区域的积累。表面性质对这种纳米颗粒的积累选择性和强度的影响主要不清楚。因此,使用不同的表面活性剂(聚山梨酯 20、十二烷基硫酸钠、胆酸钠、十六烷基三甲基溴化铵、聚乙烯醇)通过乳化溶剂蒸发技术制备了大小约为 200nm 的颗粒。在小鼠结肠炎模型中,与健康肠道相比,用聚山梨酯 20 作为表面活性剂制备的颗粒在结肠炎症区域的颗粒含量高 34.8 倍,与用十二烷基硫酸钠制备的颗粒相比,在炎症部位的颗粒含量增加了 4.5 倍。当将倍他米松包封在这样的纳米颗粒中时,这种效果也转化为显著更高的缓解效果。本研究表明表面性质对实验性结肠炎的被动靶向方法的重要性。这种影响似乎与颗粒大小的影响同样重要。