pH-responsive in situ gelation via phenylboronate-glucamine ester-crosslinking in modified hyaluronan at physiological pH

IF 2.3 4区化学 Q3 CHEMISTRY, PHYSICAL

Colloid and Polymer Science Pub Date : 2025-07-02 DOI:10.1007/s00396-025-05463-y

Ryotaro Miki, Tsutomu Yamaki, Masaki Uchida, Hideshi Natsume

{"title":"pH-responsive in situ gelation via phenylboronate-glucamine ester-crosslinking in modified hyaluronan at physiological pH","authors":"Ryotaro Miki, Tsutomu Yamaki, Masaki Uchida, Hideshi Natsume","doi":"10.1007/s00396-025-05463-y","DOIUrl":null,"url":null,"abstract":"<div><p>In situ gelling materials that rapidly form gels upon contact with body fluids are highly attractive for clinical applications. Boronate ester-crosslinked materials can create flexible, pH-responsive hydrogels. In this study, we focused on glucamine as the <i>cis-</i>diol-containing moiety in phenylboronic acid (BA) derivatives. We developed a modified hyaluronan acidic system composed of BA derivative-modified hyaluronan and glucamine-modified hyaluronan. 3-Amino-4-fluorophenylboronic acid and D-glucamine were modified onto sodium hyaluronate through condensation reaction, and mixed modified hyaluronan systems were prepared. We investigated the effect of pH on the rheological properties of the modified hyaluronan system and examined the binding constants (<i>K</i>) between BA derivatives and glucamine. The mixed modified hyaluronan system (pH 3.9) which combined the higher degree of substitution gelled quickly upon injection into a buffer solution at pH 7.4. The system exhibits significant pH dependence, with gelling properties increasing markedly as the pH rises from 4.4 to 7.4. For glucamine, the <i>K</i> values increased as the pD rose from 5.8 to 8.3. We concluded that successful pH-responsive in situ gelation requires a high degree of polymer substitution and strong <i>K</i> values between the BA derivative and the <i>cis</i>-diol moiety. Glucamine was identified as an effective <i>cis</i>-diol-containing moiety for BA derivatives.\n</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":520,"journal":{"name":"Colloid and Polymer Science","volume":"303 10","pages":"2073 - 2083"},"PeriodicalIF":2.3000,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00396-025-05463-y.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Colloid and Polymer Science","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s00396-025-05463-y","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}

引用次数: 0

Abstract

In situ gelling materials that rapidly form gels upon contact with body fluids are highly attractive for clinical applications. Boronate ester-crosslinked materials can create flexible, pH-responsive hydrogels. In this study, we focused on glucamine as the cis-diol-containing moiety in phenylboronic acid (BA) derivatives. We developed a modified hyaluronan acidic system composed of BA derivative-modified hyaluronan and glucamine-modified hyaluronan. 3-Amino-4-fluorophenylboronic acid and D-glucamine were modified onto sodium hyaluronate through condensation reaction, and mixed modified hyaluronan systems were prepared. We investigated the effect of pH on the rheological properties of the modified hyaluronan system and examined the binding constants (K) between BA derivatives and glucamine. The mixed modified hyaluronan system (pH 3.9) which combined the higher degree of substitution gelled quickly upon injection into a buffer solution at pH 7.4. The system exhibits significant pH dependence, with gelling properties increasing markedly as the pH rises from 4.4 to 7.4. For glucamine, the K values increased as the pD rose from 5.8 to 8.3. We concluded that successful pH-responsive in situ gelation requires a high degree of polymer substitution and strong K values between the BA derivative and the cis-diol moiety. Glucamine was identified as an effective cis-diol-containing moiety for BA derivatives.

Graphical Abstract

查看原文本刊更多论文

在生理pH下，通过苯基硼酸-氨基葡萄糖酯-交联改性透明质酸进行pH响应的原位凝胶化

在与体液接触后迅速形成凝胶的原位凝胶材料在临床应用中具有很高的吸引力。硼酸酯交联材料可以制成柔性的、ph值敏感的水凝胶。在本研究中，我们重点研究了苯硼酸（BA）衍生物中含有顺式二醇的氨基葡萄糖。研制了由BA衍生物-改性透明质酸和氨基葡萄糖-改性透明质酸组成的改性透明质酸体系。通过缩合反应将3-氨基-4-氟苯硼酸和d -氨基葡萄糖胺改性为透明质酸钠，制备了混合改性透明质酸体系。研究了pH对改性透明质酸体系流变学性质的影响，并测定了BA衍生物与氨基葡萄糖的结合常数(K)。混合修饰透明质酸体系（pH 3.9）结合了较高取代度，在pH 7.4的缓冲溶液中注射后迅速凝胶化。该体系表现出明显的pH依赖性，当pH值从4.4上升到7.4时，胶凝性能显著提高。葡萄糖胺的K值随pD从5.8升高到8.3而升高。我们得出结论，成功的ph响应原位凝胶化需要高度的聚合物取代和BA衍生物和顺式二醇部分之间的强K值。葡萄糖胺被确定为BA衍生物中有效的顺式二醇。图形抽象

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Colloid and Polymer Science 化学-高分子科学

CiteScore

4.60

自引率

4.20%

发文量

111

审稿时长

2.2 months

期刊介绍： Colloid and Polymer Science - a leading international journal of longstanding tradition - is devoted to colloid and polymer science and its interdisciplinary interactions. As such, it responds to a demand which has lost none of its actuality as revealed in the trends of contemporary materials science.