School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, United Kingdom.
Biomacromolecules. 2010 Jan 11;11(1):120-5. doi: 10.1021/bm9009667.
The viscous mucus coating that adheres to the epithelial surfaces of mammalian organs provides protection for the underlying tissues and is an efficient barrier to drug delivery. Pulsed-gradient spin-echo NMR and small-angle neutron scattering have been used to study the aqueous solution interaction of various model polymer therapeutics with mucin, the principle organic component within mucus. Nonionic polymers such as linear and star-branched poly(ethylene oxide) (PEO) and dextrin showed no appreciable interaction with mucin but suffered a moderate retardation in their rate of diffusion through the mucin solution. A strong interaction with mucin was observed for a series of polyamidoamine (PAMAM) dendrimers and hyperbranched poly(ethylene imine) (PEI), which displayed a characteristic pH-dependent profile and led to significant reductions in their rates of diffusion. These observations have implications for the design of optimized polymer therapeutic structures being adopted for the delivery of therapeutic moieties through mucin-rich environments.
黏附在哺乳动物器官上皮表面的粘性黏液层为下面的组织提供了保护，并且是药物输送的有效屏障。脉冲梯度自旋回波 NMR 和小角中子散射已被用于研究各种模型聚合物治疗剂与黏蛋白（黏液中的主要有机成分）在水溶液中的相互作用。非离子聚合物，如线性和星形支化聚（氧化乙烯）（PEO）和糊精，与黏蛋白没有明显的相互作用，但在通过黏蛋白溶液的扩散速率上受到适度的延迟。一系列聚酰胺胺（PAMAM）树枝状聚合物和超支化聚（亚乙基亚胺）（PEI）与黏蛋白表现出强烈的相互作用，呈现出特征性的 pH 依赖性特征，导致它们的扩散速率显著降低。这些观察结果对于设计经过优化的聚合物治疗结构具有重要意义，这些结构被用于通过富含黏蛋白的环境传递治疗性分子。
