Walter Franziska, Schöll Isabella, Untersmayr Eva, Ellinger Adolf, Boltz-Nitulescu George, Scheiner Otto, Gabor Franz, Jensen-Jarolim Erika
Department of Pathophysiology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria.
Biochem Biophys Res Commun. 2004 Mar 5;315(2):281-7. doi: 10.1016/j.bbrc.2004.01.057.
In this study, we constructed particles applicable for oral immunotherapy of type I allergy by protecting allergens from digestion and supporting intestinal antigen uptake. Therefore, birch-pollen allergens were entrapped in poly(d,l-lactic-co-glycolic acid) microspheres by spray-drying rendering microspheres with a main population of 1-3microm. Microspheres were further coated with wheat germ agglutinin (WGA) to target enterocytes. Coating with WGA did not alter the surface characteristics of the microspheres as demonstrated in scanning electron microscopy. Binding of WGA was specific and could be inhibited by chitotriose to 14.7+/-6.9%. Comparable amounts of allergen were released from both particle-types with 46.3+/-1.7% and 44.5+/-2.6% during 21 days. Simulating gastric digestion in vitro, antigenicity of allergens entrapped in WGA-microspheres was preserved to 59.8+/-1.5% even after 2h. Feedings of BALB/c mice with WGA-microspheres induced higher levels of allergen-specific IgG-levels than gavages of uncoated microparticles or naked protein. Thus, we conclude that WGA-microspheres are suitable vehicles for oral delivery and mucosal targeting due to lectin-mediated bioadhesion.
在本研究中，我们通过保护变应原不被消化并促进肠道抗原摄取，构建了适用于I型过敏口服免疫疗法的微粒。因此，通过喷雾干燥将桦树花粉变应原包裹于聚（d，l-乳酸-乙醇酸）微球中，制成主要粒径为1-3微米的微球。微球进一步用麦胚凝集素（WGA）包被以靶向肠上皮细胞。扫描电子显微镜显示，用WGA包被并未改变微球的表面特征。WGA的结合是特异性的，可被壳三糖抑制至14.7±6.9%。两种类型的微粒在21天内释放出相当数量的变应原，分别为46.3±1.7%和44.5±2.6%。在体外模拟胃消化过程中，即使经过2小时，WGA微球中包裹的变应原的抗原性仍保留至59.8±1.5%。用WGA微球喂食BALB/c小鼠比用未包被的微粒或裸露蛋白灌胃诱导出更高水平的变应原特异性IgG。因此，我们得出结论，由于凝集素介导的生物黏附作用，WGA微球是口服给药和黏膜靶向的合适载体。
