Tunable PEG-Azlactone Hydrogels Enable Programmable Multiphase Drug Delivery

Authors

• Emily Rasmussen, University of Mississippi
• S. K.Arif Mohammad, University of Mississippi
• Kendall Kelly, University of Mississippi
• Ally Grace Bounds, University of Mississippi
• Kenneth Hulugalla, University of Mississippi
• Penelope Jankoski, University of Southern Mississippi
• Evan Stacy, University of Southern Mississippi
• William L. Jarrett, University of Southern Mississippi
• Tristan Clemons, University of Southern Mississippi
• Adam E. Smith, University of Mississippi
• Thomas A. Werfel, University of MississippiFollow

Document Type

Article

Publication Date

6-8-2026

Abstract

New therapeutic regimens increasingly rely on coordinated, time-dependent delivery of multiple agents, placing new demands on biomaterials capable of precisely regulating release profiles. In this work, azlactone-functional polymers were cross-linked with poly(ethylene glycol) (PEG) to create a tunable hydrogel platform in which cross-linking density and PEG-diol to PEG-diamine ratio (PEG–OH:PEG-NH) regulate network stability, hydrolytic degradation, and release kinetics. Herein, we evaluate how hydrogel composition influences network characteristics, degradation behavior, and the release of structurally diverse cargos, including small molecules, proteins, and nanoparticles. Across formulations, increasing PEG–OH:PEG-NH accelerated hydrolytic degradation, while decreasing cross-linking density expanded the initial mesh, together leading to differences in release kinetics. These programmable relationships enabled phased, multicargo release of small molecules and antibodies from the same hydrogel. Together, these findings highlight PEG-azlactone hydrogels as a promising platform for programmable, phased delivery of diverse therapeutic cargos.

Publication Title

Biomacromolecules

Volume

27

Issue

6

First Page

3675

Last Page

3685

Recommended Citation

Rasmussen, E., Mohammad, S., Kelly, K., Bounds, A., Hulugalla, K., Jankoski, P., Stacy, E., Jarrett, W., Clemons, T., Smith, A., Werfel, T. (2026). Tunable PEG-Azlactone Hydrogels Enable Programmable Multiphase Drug Delivery. Biomacromolecules, 27(6), 3675-3685.
Available at: https://aquila.usm.edu/fac_pubs/22128