Two-level delivery systems (DSs) for oral administration of therapeutic proteins and peptides were developed. The first level consists of outer walls of Lycopodium clavatum spores (sporopollenin exine capsules, SECs) with included target objects; the alginate microgranules serve as the second (outer) level. Alginate (a pH-dependent natural polymer) protects peptides from gastric acidity and enzyme exposure and provides slow release of target objects in an alkaline intestinal medium. Introducing ovomucoid (a peptidase inhibitor) into alginate coatings prevents enzymatic hydrolysis of peptide objects in the intestinal medium. The elemental composition of spores and SECs was controlled using energy-dispersion spectroscopy and combustion analysis; their morphology was visualized by SEM. The efficiencies of different methods of SEC loading were compared. It was demonstrated that the load value was controlled by molecular mass and the value of the isoelectric point of target objects. A comparison of peptide in vitro release profiles from DSs of various structures into simulated gastric and intestinal fluids was carried out. The mechanism of peptide release from two-level DSs was suggested. SECs were found in rat blood after intragastric administration of the two-level DSs. Time profiles of therapeutic peptide release were obtained in vivo.

中文翻译：

---

两级递送系统，用于基于头孢石藻孢子胶囊口服给药肽和蛋白质

开发了用于口服治疗性蛋白质和肽的两级递送系统（DSs）。第一层由石蒜兰的外壁组成包括目标物在内的孢子（孢子粉外膜胶囊，SEC）；藻酸盐微粒充当第二（外部）级别。海藻酸盐（一种依赖于pH值的天然聚合物）可保护肽免受胃酸和酶的侵害，并在碱性肠介质中缓慢释放目标物体。在藻酸盐涂层中引入卵粘液（一种肽酶抑制剂）可防止肠介质中肽对象的酶水解。孢子和SEC的元素组成使用能量色散光谱法和燃烧分析法进行控制。通过SEM观察它们的形态。比较了SEC加载不同方法的效率。结果表明，载荷值受分子质量和目标物体等电点值的控制。肽的比较进行了从各种结构的DS到模拟胃液和肠液的体外释放曲线。提出了从二级DS释放肽的机制。胃内注射两种水平的DS后，在大鼠血液中发现了SEC。在体内获得了治疗性肽释放的时间图。