Madsen F, Eberth K, Smart J D
Department of Analytical and Pharmaceutical Chemistry, The Royal Danish School of Pharmacy, Copenhagen.
Biomaterials. 1998 Jun;19(11-12):1083-92. doi: 10.1016/s0142-9612(98)00037-4.
The ability of mucoadhesive materials to produce a large increase in the resistance to deformation when incorporated into a mucus gel, relative to when the mucus gel and test materials are evaluated separately at the same concentration, has been reported in several previous studies. It has been proposed that this phenomenon, termed rheological synergism, can be used as a measure of the strength of the mucoadhesive interaction. This study investigated the interactions between four putative mucoadhesive polymers (Noveon, Pemulen TR-2, carageenan and sodium carboxymethylcellulose) and a homogenised mucus gel, using dynamic oscillatory rheology. It was shown that, with the exception of sodium carboxymethylcellulose, incorporating a mucoadhesive polymer into a mucus gel produces rheological behaviour indicative of a weakly cross-linked gel network, which suggested a structure containing physical chain entanglements and non-covalent (probably hydrogen) bonds. Optimum gel strengthening occurred in a weakly acidic environment, suggesting an optimum conformation and degree of ionisation of the polymer and mucus molecules. Subsequent work suggested that the macromolecular interactions between polymer and mucus are sensitive to temperature, with the dynamic moduli decreasing with increasing temperature, further indicating bonding of a non-covalent nature. This work provide further evidence that rheological methods can be used as a tool to evaluate the interactions between a mucoadhesive macromolecule and a mucus gel. It also adds to the perception that molecular interpenetration may be an important factor in mucoadhesion by strengthening the mucus in the mucoadhesive/mucosal interfacial layer.
相对于在相同浓度下分别评估黏液凝胶和测试材料时，当将黏膜黏附材料掺入黏液凝胶中时，其产生的抗变形能力大幅增加，这一现象在先前的多项研究中已有报道。有人提出，这种被称为流变协同作用的现象可作为衡量黏膜黏附相互作用强度的一种方法。本研究使用动态振荡流变学，研究了四种假定的黏膜黏附聚合物（诺誉、Pemulen TR-2、角叉菜胶和羧甲基纤维素钠）与均质化黏液凝胶之间的相互作用。结果表明，除羧甲基纤维素钠外，将黏膜黏附聚合物掺入黏液凝胶中会产生表明存在弱交联凝胶网络的流变行为，这表明其结构包含物理链缠结和非共价（可能是氢键）键。在弱酸性环境中发生了最佳的凝胶强化，这表明聚合物和黏液分子具有最佳构象和电离程度。后续研究表明，聚合物与黏液之间的大分子相互作用对温度敏感，动态模量随温度升高而降低，这进一步表明存在非共价性质的键合。这项工作提供了进一步的证据，证明流变学方法可作为评估黏膜黏附大分子与黏液凝胶之间相互作用的工具。它还加深了人们的认识，即分子互穿可能是通过强化黏膜黏附/黏膜界面层中的黏液而在黏膜黏附中起重要作用的一个因素。
