Extreme pH Tolerance in Peptide Coacervates Mediated by Multivalent Hydrogen Bonds for Enzyme-Triggered Oral Drug Delivery
Shujun Chen, Guijin Zou, Qi Guo, Xuliang Qian, Haopeng Li, Huajian Gao, Jing Yu
Abstract
Biopolymer-based complex coacervates hold promising prospects in the field of biomedicine. However, their low stability in environments with extreme pH and high salt concentrations, largely due to weakly charged biomacromolecules and insufficient understanding of their assembly processes, has hindered their practical applications in oral drug delivery. Here, we have developed Dopa-containing peptide-based complex coacervates that are stable across a wide range of pH (1-11) and salt concentrations. Large-scale all-atom molecular dynamics simulations reveal that multivalent hydrogen bonds control the assembly pathway of the coacervates and boost their stability. Systematic point mutations reveal that various multivalent molecular interactions can synergistically tune the properties of complex coacervates. Such peptide coacervates show high drug encapsulation efficacy and trypsin-triggered release, presenting great potential for oral drug delivery applications. Our multivalent hydrogen bond-mediated peptide coacervates provide new design principles of engineering functional coacervates for diverse applications.