Enhancement of poly(ethylene glycol) mucoadsorption by biomimetic end group functionalization
Enhancement of poly(ethylene glycol) mucoadsorption by biomimetic end group functionalization
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DOI：
10.1116/1.2422894
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发表时间：
2006-12-01
期刊：
影响因子：
2.1
通讯作者：
Messersmith, Phillip B.
中科院分区：
文献类型：
--
作者：
Catron, Nathaniel D.;Lee, Haeshin;Messersmith, Phillip B.
聚（乙二醇）（PEG）广泛用于制药、生物技术和医疗器械行业。尽管PEG是一种生物相容性聚合物，在药物递送技术中得到了广泛的应用，但它不被认为是对粘膜组织的粘合剂。在这里，作者描述了一种简单的方法，通过端基官能化与氨基酸3，4-二羟基苯基-L-丙氨酸（多巴），以提高PEG聚合物的粘膜吸附。使用各种表面分析技术，作者表明，在每个臂的末端用单个DOPA残基官能化的四臂聚（乙二醇）聚合物（PEG-（DOPA）（4））强烈吸附到表面固定的粘蛋白上。证明了PEG-（DOPA）（4）在4.5至8.5的几个pH值范围内的成功粘膜吸附，并且用未官能化的四臂PEG的对照实验证明PEG-（DOPA）（4）的粘膜吸附主要是由于DOPA端基的存在。这一结论得到了单分子原子力显微镜实验的证实，该实验揭示了多巴和吸附的粘蛋白之间令人惊讶的371 +/- 93 pN的强相互作用力。与已知的粘膜粘附聚合物的直接比较显示，PEG（DOPA）（4）对固定化粘蛋白的吸附性等于或大于这些现有的粘膜粘附聚合物。除了证明DOPA功能化显著增强PEG的粘膜粘附特性之外，本研究还介绍了一种用于快速筛选粘膜粘附聚合物的新的简单方法。(c)2006年美国真空学会。
Poly (ethylene glycol) (PEG) is widely used in the pharmaceutical, biotechnology, and medical device industries. Although PEG is a biocompatible polymer that has enjoyed widespread use in drug delivery technology, it is not considered adhesive toward mucosal tissue. Here the authors describe a simple approach to enhancing mucoadsorption of PEG polymers through end group functionalization with the amino acid 3,4-dihydroxyphenyl-L-alanine (DOPA) . Using a variety of surface analytical techniques, the authors show that a four-armed poly(ethylene glycol) polymer functionalized with a single DOPA residue at the terminus of each arm (PEG-(DOPA)(4)) adsorbed strongly to surface immobilized mucin. Successful mucoadsorption of PEG-(DOPA)(4) across several pH values ranging from 4.5 to 8.5 was demonstrated, and control experiments with unfunctionalized four-arm PEG demonstrated that mucoadsorption of PEG-(DOPA)(4) is due largely to the presence of DOPA end groups. This conclusion was confirmed with single molecule atomic force microscopy experiments that revealed a surprisingly strong interaction force of 371 +/- 93 pN between DOPA and adsorbed mucin. Direct comparisons with known mucoadhesive polymers revealed that PEG(DOPA)(4) was equal to or more adsorptive to immobilized mucin than these existing mucoadhesive polymers. In addition to demonstrating significant enhancement of mucoadhesive properties of PEG by DOPA functionalization, this study also introduced a new simple approach for rapid screening of mucoadhesive polymers. (c) 2006 American Vacuum Society.