Long-Term Stabilization and Storage of Peptide-Based Coacervate through Tyrosine-Rich Sequences and Polyphenol Network.

Abstract

Peptide-based coacervates are biocompatible and tunable but inherently unstable due to weak, reversible noncovalent interactions, making them vulnerable to stress from pH and temperature. This is especially difficult for coacervates used in commercial products with low-temperature storage or lyophilization. We engineered lyophilization-tolerant nanocoacervates by incorporating aromatic tyrosine residues into oligopeptide [(YR)₂R₁₀ + (YR)₂D₁₀] and reinforcing them with tannic acid (TA). This approach leverages π-π stacking, cation-π interactions, hydrogen bonds, and electrostatic interactions to create a stabilized network. The coacervates maintain their structure, count (10⁷ particles/mL), size (<500 nm), and morphology after exposure to ionic strength of 10-100 mM, pH 3-10, elevated temperatures of 25-80 °C, biological media, and, crucially, freeze drying/rehydration. The study confirms that all interactions are essential for recovery from lyophilization. This is the first peptide-based coacervate system with lyophilization tolerance, supporting scalable applications in drug delivery, biostabilization, and regenerative medicine without cold-chain storage.