Amino Acid-based Coacervates with Tunable Stimulus-Responsive Properties for Enhanced Acute Colitis Therapy

Area of Science:

• Biomaterials science
• Chemical biology
• Biomedical engineering

Background:

• Biomolecular condensates are vital for cellular organization and biomedicine.
• Limited pH stability of condensates restricts their use in diverse physiological settings.
• Developing pH-stable biomolecular systems is crucial for advanced biomedical applications.

Purpose of the Study:

• To engineer tunable coacervates from simple amino acids with broad pH stability.
• To investigate the thermoresponsive properties of these novel amino acid-based coacervates.
• To demonstrate the potential of pH-stable coacervates for in vivo drug delivery and therapy.

Main Methods:

• A molecular shielding strategy was employed to modify terminal ionizable groups of amino acids.
• Selective modification was used to create phase behavior independent of environmental pH.
• Coacervates were characterized for pH stability, thermoresponsive transitions (LCST/UCST), and in vivo performance.

Main Results:

• Tunable coacervation of simple amino acids was achieved over a wide pH range (1.0-13.0).
• The amino acid-based coacervates exhibited distinct thermoresponsive behaviors (LCST or UCST).
• N-terminal shielded phenylalanine coacervates demonstrated stability in gastric conditions and prolonged gastrointestinal drug retention.

Conclusions:

• Molecular shielding offers a method to create pH-independent amino acid coacervates.
• These programmable coacervates possess tunable thermoresponsive features for tailored applications.
• The study demonstrates successful in vivo oral drug delivery and therapy for acute colitis, highlighting potential for biomedical applications.