Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion - Israel Institute of Technology, Haifa, 3200003, Israel.
Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, 3200003, Israel.
Macromol Biosci. 2024 Jul;24(7):e2400028. doi: 10.1002/mabi.202400028. Epub 2024 Mar 28.
Mucosal tissues represent a major interface between the body and the external environment and are covered by a highly hydrated mucins gel called mucus. Mucus lubricates, protects and modulates the moisture levels of the tissue and is capitalized in transmucosal drug delivery. Pharmaceutical researchers often use freshly excised animal mucosal membranes to assess mucoadhesion and muco-penetration of pharmaceutical formulations which may struggle with limited accessibility, reproducibility, and ethical questions. Aiming to develop a platform for the rationale study of the interaction of drugs and delivery systems with mucosal tissues, in this work mucus-mimicking mucin-based hydrogels are synthesized by the tandem chemical and physical crosslinking of mucin aqueous solutions. Chemical crosslinking is achieved with glutaraldehyde (0.3% and 0.75% w/v), while physical crosslinking by one or two freeze-thawing cycles. Hydrogels after one freeze-thawing cycle show water content of 97.6-98.1%, density of 0.0529-0.0648 g cm⁻, and storage and loss moduli of ≈40-60 and ≈3-5 Pa, respectively, that resemble the properties of native gastrointestinal mucus. The mechanical stability of the hydrogels increases over the number of freeze-thawing cycles. Overall results highlight the potential of this simple, reproducible, and scalable method to produce artificial mucus-mimicking hydrogels for different applications in pharmaceutical research.
黏膜组织是人体与外部环境之间的主要接口，由一种高度水合的黏蛋白凝胶（称为黏液）覆盖。黏液具有润滑、保护和调节组织水分水平的作用，在跨黏膜药物传递中具有重要作用。制药研究人员通常使用新鲜切除的动物黏膜膜来评估药物制剂的黏膜黏附性和黏膜穿透性，但这种方法存在可及性有限、重现性差和伦理问题等挑战。本工作旨在开发一种平台，用于合理研究药物和传递系统与黏膜组织的相互作用，通过化学和物理交联的串联方法合成了模拟黏液的黏蛋白水凝胶。化学交联是通过戊二醛（0.3%和 0.75% w/v）实现的，而物理交联是通过一次或两次冻融循环实现的。经过一次冻融循环的水凝胶的含水量为 97.6-98.1%，密度为 0.0529-0.0648 g cm⁻³，储能模量和损耗模量分别约为 40-60 和 3-5 Pa，类似于天然胃肠道黏液的性质。水凝胶的机械稳定性随冻融循环次数的增加而增加。总体结果表明，这种简单、可重复且可扩展的方法具有生产用于制药研究中不同应用的人工模拟黏液水凝胶的潜力。
