Undergraduate Researcher University of Mississippi Tupelo, Mississippi, United States
Introduction: Recent advances in programmable hydrogels have significantly impacted drug delivery and tissue engineering, with particular promise for immunotherapy. Immunotherapies often suffer from poor pharmacokinetics and off-target effects, and require precise control over drug release profiles to maximize efficacy. Our study introduces a novel approach using poly(2-vinyl-4,4-dimethylazlactone) (PVDMA) combined with diamine and diol-functionalized polyethylene glycol (PEG) to create a hydrogel with programmable release characteristics. This hydrogel allows for the dual delivery of agents, featuring both rapid release of small molecules and sustained release of antibodies. By incorporating polyoxyethylene bis(amine) (PEG-NH) as a hydrolytically stable linker and polyethylene glycol (PEG-OH) as a hydrolytically-degradable linker , we achieve controlled degradation and release for multiple model therapeutics. Furthermore, we synthesized hydrogel capable of multimodal release with sequential independent release rates of a small molecule and antibody.
Materials and
Methods: The VDMA monomer was synthesized by reversible addition−fragmentation chain-transfer (RAFT) polymerization to create a well-defined, monodisperse polymer. PVDMA was mixed with varying ratios of PEG-NH and PEG-OH to create a crosslinked polymer network and fluorescent model therapeutics were incorporated during mixing at room temperature. The synthesized hydrogel was placed in a buffer solution and the fluorescence measured to determine their release profiles.
Results, Conclusions, and Discussions: Successful synthesis of PVDMA was verified via 1H NMR and GPC and hydrogel structure was characterized via FTIR and PFG-NMR. Release profiles demonstrated fast diffusion for small molecules, slow diffusion for polymer-drug conjugates, and degradation controlled release for proteins . Protein release rates varied depending on the hydrogel composition. Effective sequential release was demonstrated with burst release of small molecules followed by sustained release of antibody. The release of model therapeutics was controlled by adjusting the density and composition of hydrogel linkers. These findings demonstrate the potential of the synthesized programmable hydrogel for efficient and controlled delivery of various therapeutic agents. The sequential release of two different classes of drugs presents a platform well suited for immunotherapeutic delivery. The ability to control release of therapeutics across drug classes provides an exciting opportunity for the development of multifunctional therapies that can be leveraged to produce a specific, localized immune response. Overall, the programmable gel provides a promising platform for the development of advanced materials with tunable degradability and controlled release capability for various biomedical applications. Future work will further tune the hydrogels to incorporate precise dosages of immunotherapeutic drugs and test their release in vitro and in vivo.
Acknowledgements (Optional): This material is based upon work supported by the NSF Grant CAREER 2141666. I would like to thank the Biomedical Engineering Department at the University of Mississippi, the interdisciplinary NanoBioSciences Lab (iNBS), and the NIEC Core lab for their support and BMES for this opportunity.
