(H-305) Synthesis of Programable Hydrogel at Room Temperature with Tuneable Release for Various Delivery Applications

Introduction:: Programmable hydrogels with tuneable release profiles have garnered significant interest in recent years due to their versatile applications in drug delivery and tissue engineering. The precise spatiotemporal control provided by hydrogels is important to facilitate a desired response without deleterious side effects, especially in immunotherapies. Such hydrogels can be designed to encapsulate the range of drug classes, from biologics to small molecules, with different release profiles dependent on the hydrogel composition. In this study, we report a novel method for synthesizing a programmable hydrogel with tuneable degradability and release using poly(2-vinyl-4,4-dimethylazlactone) (PVDMA) combined with diamine and diol-functionalized polyethylene glycol (PEG) crosslinkers sensitive to pH mediated cleavage.

Materials and Methods:: The VDMA monomer was polymerized via reversible addition fragmentation chain transfer (RAFT) polymerization to yield a well-defined, mono dispersed polymer. The PVDMA scaffold was constructed by mixing PVDMA with PEG diamine and diol crosslinkers without stirring or heating. The hydrogels were incubated in buffer solution and their weight routinely measured to construct degradation profiles. In some cases, model therapeutics tagged with fluorophores were loaded into the hydrogels during mixing. The loaded PVDMA hydrogels were incubated in buffer solution, and the release profiles of the tagged model therapeutics were determined for different PVDMA hydrogel compositions.

Results, Conclusions, and Discussions:: Results: The successful synthesis of PVDMA was verified through ¹H NMR and FTIR spectroscopy, while the hydrogel structure was characterized using FTIR spectroscopy. We determined degradation of partially and fully crosslinked hydrogels via mass measurements. Hydrogels with 50% crosslinking exhibited faster degradation than the 100% crosslinked polymers for each crosslinking ratio. The hydrogels with greater diamine crosslinker ratio exhibited slower degradation. Interestingly, the 100% crosslinked mixture with 90:10 diol:diamine ratio and the 50% crosslinked mixture with 70:30 diol:diamine ratio did not form a hydrogel.

Discussion: The degradation and release of model therapeutics was controlled by adjusting the ratio of diol to diamine crosslinking within the hydrogel scaffold. Hydrogels with higher amine crosslinking exhibited slower degradation and potentially slower therapeutic release compared to those with lower amine crosslinking. These findings demonstrate the potential of the synthesized programmable hydrogel for efficient and controlled delivery of various therapeutic agents.

Conclusion: 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 hydrogel provides a promising platform for the development of advanced materials with tuneable degradability and controlled release capability for various biomedical applications. Future work will combine these tuneable hydrogels into a multi-layered scaffold capable of sequential delivery.


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