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

Amine-modified four- and eight-armed poloxamines were prepared and subsequently functionalized with maleimide or fury' groups. Aqueous solutions of these polymers exhibited an immediate gelation at a temperature above 37 C. Concomitantly, Diets 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.