Mechanically Enhanced Ultrashort Peptide Hydrogels for pH-Triggered Release.

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Biomaterials Engineering

Background:

• Ultrashort peptide hydrogels are promising soft materials but face challenges in solubility and gelation at physiological conditions.
• Conventional Fmoc-dipeptides like Fmoc-FF are effective hydrogelators but require precise control for injectable applications.
• Developing injectable and in situ forming peptide hydrogels necessitates overcoming limitations in solubility and responsiveness.

Purpose of the Study:

• To design and characterize a pH-responsive injectable hydrogel based on a novel ultrashort peptide.
• To utilize the protonation-deprotonation equilibrium of a pyridyl moiety as a molecular switch for hydrogel formation and disassembly.
• To investigate the potential of this hydrogel system for controlled drug release applications.

Main Methods:

• Synthesis of a dipeptide incorporating Fmoc-β-(3-pyridyl)-l-alanine (Fmoc-3-Pal-OH).
• Comprehensive characterization using fluorescence spectroscopy, circular dichroism, FTIR, SEM, and rheology.
• Evaluation of pH-dependent self-assembly, mechanical properties, and drug release kinetics (curcumin).

Main Results:

• The Fmoc-3-Pal-OH dipeptide forms hydrogels spontaneously between pH 6.0-8.0, with disassembly at acidic pH.
• pH modulation allows fine control over nanofibrillar organization, viscoelasticity, and mechanical stability.
• The hydrogel demonstrated high loading capacity for curcumin and sustained release at neutral pH, with accelerated release at acidic pH.

Conclusions:

• A simple and robust molecular design strategy was achieved for pH-responsive ultrashort peptide hydrogels.
• Protonation-controlled self-assembly overcomes limitations of conventional Fmoc-based hydrogelators.
• These adaptable peptide networks show significant potential for stimuli-responsive soft materials and advanced drug delivery systems.