Peptide hydrogels for affinity-controlled release of therapeutic cargo: Current and potential strategies

The development of devices for the precise and controlled delivery of therapeutics has grown rapidly over the last few decades. Drug delivery materials must provide a depot with delivery profiles that satisfy pharmacodynamic and pharmacokinetic requirements resulting in clinical benefit. Therapeutic efficacy can be limited due to short half-life and poor stability. Thus, to compensate for this, frequent administration and high doses are often required to achieve therapeutic effect, which in turn increases potential side effects and systemic toxicity. This can potentially be mitigated by using materials that can deliver drugs at controlled rates, and material design principles that allow this are continuously evolving. Affinity-based release strategies incorporate a myriad of reversible interactions into a gel network, which have affinities for the therapeutic of interest. Reversible binding to the gel network impacts the release profile of the drug. Such affinity-based interactions can be modulated to control the release profile to meet pharmacokinetic benchmarks. Much work has been done developing affinity-based control in the context of polymer-based materials. However, this strategy has not been widely implemented in peptide-based hydrogels. Herein, we present recent advances in the use of affinity-controlled peptide gel release systems and their associated mechanisms for applications in drug delivery.