Nanofibrous supramolecular peptide hydrogels for controlled release of small-molecule drugs and biologics

Maintaining safe and potent drug levels in vivo is challenging. Multidomain peptides assemble into supramolecular hydrogels with a well-defined, highly porous nanostructure that makes them attractive for drug delivery. However, their ability to extend release is typically limited by rapid drug diffusion. Here, to overcome this challenge, we present self-assembling boronate ester release (SABER) multidomain peptides capable of engaging in dynamic covalent bonding with payloads containing boronic acids. As examples, we demonstrate that SABER hydrogels can prolong the release of boronic acid-containing small-molecule drugs and boronic acid-modified biologics such as insulin and antibodies. Pharmacokinetic studies reveal that SABER hydrogels extend the therapeutic effect of ganfeborole from days to weeks, preventing Mycobacterium tuberculosis growth compared with oral administration in an infection model. Similarly, SABER hydrogels extended insulin activity, maintaining normoglycemia for 6 days in diabetic mice after a single injection. These results suggest that SABER hydrogels present broad potential for clinical translation.