Reaching Increased Hydrogel Stability In Vivo through β-Hairpin Peptide-Based Hydrogels.

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Peptide Chemistry

Background:

• Peptide-based hydrogels offer versatile and biocompatible platforms for pharmaceutical and biomedical uses.
• Beta-hairpin designs improve beta-strand alignment and control hydrogel physicochemical properties.

Purpose of the Study:

• To design and evaluate beta-hairpin hydrogelators using P1-based hexamer strands.
• To assess the impact of a fluorinated proline surrogate (CF3-ΨPro) on hairpin stabilization and hydrogel properties.
• To investigate the in vivo stability and drug release potential of novel beta-hairpin hydrogels.

Main Methods:

• Synthesis and characterization of beta-hairpin peptide hydrogelators.
• Evaluation of physicochemical, mechanical, and structural properties of hydrogels.
• In vitro drug release studies and in vivo subcutaneous injection studies in mice.

Main Results:

• Beta-hairpin hydrogels with a fluorinated proline surrogate (P17) and non-fluorinated analog (P3) showed enhanced stability.
• P3 and P17 hydrogels remained at 70% and 45% at the injection site after 11 days, respectively.
• Compared to P1 (10% after 7 days), P3 and P17 hydrogels exhibited significantly prolonged in vivo lifespan.

Conclusions:

• Beta-hairpin peptide hydrogels demonstrate potential for prolonged drug delivery applications.
• The incorporation of fluorinated proline surrogates can enhance hydrogel stability and lifespan.
• These findings support the development of advanced peptide hydrogels for sustained therapeutic release.