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

Abstract

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.

Self-Assembled Peptide Nanostructures for ECM Biomimicry

“…Readers interested in the details of their various types of design are recommended to read a recent book chapter that provides a comprehensive overview of the topic [24]. Several recent reviews also cover this area [25,26], as well as the use of enzymes to control self-assembly [27], applications for the delivery of drugs and therapeutics [28][29][30][31][32][33], proteins [34,35], and, more generally biomedical uses [36], with a specific focus on antimicrobials [37], cancer [38], and wound healing too [39].…”

An Exploration of Multiple Component Peptide Assemblies by Enzyme‐Instructed Self‐Assembly

“…Experimentation with peptide hydrogels is vast, which speaks to its ever‐growing list of examples and applications [6–40] . We reported the first use of an Fmoc based dipeptide which forms gels, and responds to a ligand‐receptor interaction [41] .…”

Leveraging Affinity Interactions to Prolong Drug Delivery of Protein Therapeutics

“…Affinity-based drug delivery systems have emerged as a popular way to help control and prolong the release of protein therapeutics [ 12 ]. Broadly, “affinity-based” delivery encompasses any matrix/guest system that leverages receptor/ligand, electrostatic/ionic, hydrogen bonding, hydrophobic, or van der Waal interactions to increase the thermodynamic interactions between the matrix host and the guest payload [ 13 , 14 , 15 ]. A well-established example of this is synthesizing a polymer matrix with exposed streptavidin sites designed to bind with biotinylated protein payloads [ 16 , 17 ].…”