Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Corrensstraße 48, 48149, Münster, Germany.
School of Food Science and Nutrition, University of Leeds, Leeds, LS2 9JT, UK.
Appl Microbiol Biotechnol. 2020 Jul;104(13):5943-5957. doi: 10.1007/s00253-020-10647-3. Epub 2020 May 12.
The first step in the development of Helicobacter pylori pathogenicity is the receptor-mediated adhesion to the gastric epithelium. Inhibition of outer membrane proteins of H. pylori (e.g. BabA) by antiadhesive drugs will contribute to reduced recolonization and infection. Pectin from apple inhibits the BabA and LPS-mediated adhesion of H. pylori to human stomach cells. Pectin-coated liposomes with encapsulated amoxicillin were characterized for polydispersity, zeta potential, encapsulation efficiency, stability, and amoxicillin release. Coated liposomes did not influence the viability of AGS and HT29-MTX cells up to 100 μg/mL but exert cytotoxicity against H. pylori at 10 μg/mL. Pectin-coating of liposomes provoked direct interaction and subsequent binding of the particles to surface structures of H. pylori, and interaction with mucus from porcine stomach and mucus secreted by HT29-MTX cells. Laser scanning microscopy of H. pylori and AGS cells together with liposomes indicated co-aggregation. The mucoadhesive effect seems interesting as stomach cells are covered by a mucus layer. H. pylori is able to penetrate and cross the mucin rapidly to reach pH-neutral epithelium to escape the acidic environment, followed by interaction with epithelial cells. In summary, all experimental evidence is consistent with a specific interaction of pectin-coated liposomes with mucins and surface structures of H. pylori. As the coated liposomes show mucoadhesion to the negatively charged mucins, docking to stomach mucin, mucus penetration, and recognition of and adhesion to H. pylori, they can be considered a novel type of multifunctional drug carriers for local antibiotic therapy against H. pylori. KEY POINTS: • Smart, multifunctional mucoadhesive liposomes • Specific targeting against BabA/LPS of Helicobacter pylori • Inhibition of bacterial adhesion of H. pylori to human host cells • Release of antibiotic cargo.
幽门螺杆菌致病性发展的第一步是受体介导的对胃上皮的黏附。抗黏附药物抑制幽门螺杆菌的外膜蛋白（例如 BabA）将有助于减少再定植和感染。苹果果胶抑制 BabA 和 LPS 介导的幽门螺杆菌与人胃细胞的黏附。用包封阿莫西林的果胶包被脂质体进行多分散性、ζ电位、包封效率、稳定性和阿莫西林释放的表征。包被的脂质体在高达 100μg/mL 时不会影响 AGS 和 HT29-MTX 细胞的活力，但在 10μg/mL 时对幽门螺杆菌表现出细胞毒性。果胶包被脂质体引起颗粒与幽门螺杆菌表面结构的直接相互作用和随后的结合，并与猪胃黏液和 HT29-MTX 细胞分泌的黏液相互作用。幽门螺杆菌和 AGS 细胞与脂质体一起的激光扫描显微镜检查表明共聚集。作为胃细胞被黏液层覆盖，这种黏液黏附效果很有趣。幽门螺杆菌能够迅速穿透和穿过黏液层到达 pH 中性的上皮细胞以逃避酸性环境，然后与上皮细胞相互作用。总之，所有实验证据都与果胶包被脂质体与黏液和幽门螺杆菌表面结构的特异性相互作用一致。由于包被的脂质体对带负电荷的黏液具有黏附性，能够停靠在胃黏液上、穿透黏液、识别和黏附幽门螺杆菌，因此它们可以被认为是一种新型的多功能药物载体，可用于针对幽门螺杆菌的局部抗生素治疗。关键点：• 智能、多功能的黏液黏附脂质体• 针对幽门螺杆菌的 BabA/LPS 的特异性靶向• 抑制幽门螺杆菌对人宿主细胞的黏附• 释放抗生素有效载荷。
