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可控抗体从可降解温敏水凝胶中释放出来,这些水凝胶由 Diels-Alder 化学交联而成。

Controlled Antibody Release from Degradable Thermoresponsive Hydrogels Cross-Linked by Diels-Alder Chemistry.

机构信息

Department of Pharmaceutical Technology, Faculty of Chemistry and Pharmacy, University of Regensburg , 93040 Regensburg, Germany.

出版信息

Biomacromolecules. 2017 Aug 14;18(8):2410-2418. doi: 10.1021/acs.biomac.7b00587. Epub 2017 Jul 6.

Abstract

Amine-modified four- and eight-armed poloxamines were prepared and subsequently functionalized with maleimide or furyl groups. Aqueous solutions of these polymers exhibited an immediate gelation at a temperature above 37 °C. Concomitantly, Diels-Alder reactions gradually cross-linked and cured the gels. Different ratios between four- and eight-armed macromonomers were used to tune hydrogel stability and mechanical properties. In this way, hydrogel stability could be precisely controlled in the range of 14 to 329 days. Controlled release of the model antibody bevacizumab was achieved over a period of 7, 21, and 115 days. Release profiles were triphasic with a low burst; approximately 87% of the released antibody was intact and displayed functional binding. The hydrogels presented in this study are degradable, nontoxic, rapidly gelling, stable, and provide controlled antibody release. They can be tailored to match the demands of various applications and present an attractive platform for antibody delivery.

摘要

胺基改性的四臂和八臂聚氧乙烯醚被制备,并随后用马来酰亚胺或呋喃基官能化。这些聚合物的水溶液在高于 37°C 的温度下立即凝胶化。同时,Diels-Alder 反应逐渐交联和固化凝胶。使用四臂和八臂大分子单体的不同比例来调节水凝胶的稳定性和机械性能。通过这种方式,可以在 14 至 329 天的范围内精确控制水凝胶的稳定性。模型抗体贝伐单抗的控释持续了 7、21 和 115 天。释放曲线呈三相,初始突释较低;约 87%的释放抗体保持完整并显示出功能结合。本研究中提出的水凝胶是可降解的、无毒的、快速凝胶化的、稳定的,并提供了对抗体的控释。它们可以根据各种应用的需求进行定制,为抗体传递提供了一个有吸引力的平台。

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