Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123 Saarbrücken, Germany.
PharmBioTec GmbH, Science Park 1 Campus D 1.1, 66123 Saarbrücken, Germany.
Adv Drug Deliv Rev. 2018 Jan 15;124:82-97. doi: 10.1016/j.addr.2017.10.009. Epub 2017 Oct 26.
A layer of mucus covers the surface of all wet epithelia throughout the human body. Mucus is a hydrogel mainly composed of water, mucins (glycoproteins), DNA, proteins, lipids, and cell debris. This complex composition yields a tenacious viscoelastic hydrogel that lubricates and protects the exposed epithelia from external threats and enzymatic degradation. The natural protective role of mucus is nowadays acknowledged as a major barrier to be overcome in non-invasive drug delivery. The heterogeneity of mucus components offers a wide range of potential chemical interaction sites for macromolecules, while the mesh-like architecture given to mucus by the intermolecular cross-linking of mucin molecules results in a dense network that physically, and in a size-dependent manner, hinders the diffusion of nanoparticles through mucus. Consequently, drug diffusion, epithelial absorption, drug bioavailability, and ultimately therapeutic outcomes of mucosal drug delivery can be attenuated.
在人体的所有湿润上皮表面都覆盖有一层黏液。黏液是一种水凝胶，主要由水、黏蛋白（糖蛋白）、DNA、蛋白质、脂质和细胞碎片组成。这种复杂的组成产生了一种坚韧的黏弹性水凝胶，可润滑和保护暴露的上皮免受外部威胁和酶的降解。目前人们已经认识到，黏液的天然保护作用是在非侵入性药物递送中需要克服的主要障碍。黏液成分的异质性为大分子提供了广泛的潜在化学相互作用位点，而黏蛋白分子的分子间交联赋予黏液的网状结构导致形成致密的网络，以尺寸依赖的方式物理地阻碍了纳米颗粒通过黏液的扩散。因此，药物扩散、上皮吸收、药物生物利用度以及黏膜药物递送的最终治疗效果都可能会减弱。
