Drug-triggered and cross-linked self-assembling nanofibrous hydrogels

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Peptide Engineering

Background:

• Multidomain peptides (MDP) self-assembly can be engineered for controlled payload release.
• Tailored payloads can modulate the extracellular environment for therapeutic applications.
• Controlled release of therapeutic agents offers precise control over in vitro and in vivo responses.

Purpose of the Study:

• To demonstrate ionic cross-linking of peptides using multivalent drugs for hydrogel formation.
• To create hydrogels for sustained long-term drug delivery.
• To investigate the utility of various multivalent anions, particularly suramin, for hydrogel formation and drug release.

Main Methods:

• Ionic cross-linking of multidomain peptides (MDP) with multivalent anions (phosphate, heparin, clodronate, trypan, suramin).
• Hydrogel characterization using scanning and transmission electron microscopy (SEM/TEM) and rheometry (G', G″).
• Drug release kinetics measured by UV spectroscopy; cellular response assessed via M1 polarization of THP-1 cells.

Main Results:

• All tested multivalent anions formed hydrogels, demonstrating a general approach.
• Suramin yielded the best hydrogels per unit concentration, forming a fibrous meshwork.
• Prolonged release of suramin over 30 days was observed, with demonstrated bioavailability and function in attenuating M1 polarization.

Conclusions:

• A novel strategy for creating polymeric delivery vehicles via ionic cross-linking of peptides with multivalent drugs was developed.
• The resulting hydrogels provide sustained long-term drug release.
• Suramin-cross-linked hydrogels effectively modulate cellular phenotype, highlighting their therapeutic potential.