Intrinsically Disordered Protein Coating for Oral Delivery of Peptide Drugs

Area of Science:

• Biomaterials Science
• Drug Delivery
• Protein Engineering

Background:

• Oral delivery of peptide therapeutics is challenging due to gastrointestinal barriers.
• Existing methods often struggle with stability and targeted release in the digestive system.

Purpose of the Study:

• To develop an engineered synthetic intrinsically disordered protein (SynIDP) for self-assembling enteric coatings.
• To enhance gastric acid resistance and intestinal targeting of peptide drugs.
• To optimize drug encapsulation and controlled release for improved oral delivery.

Main Methods:

• Designed SynIDPs mimicking native intrinsically disordered proteins (IDPs) for controlled phase transitions.
• Investigated temperature-controlled condensation and pH-controlled solidification of the protein coating.
• Analyzed phase transition kinetics to control coating morphology (nano-to-microscale).
• Tested coating protection of peptide drugs in simulated gastric conditions and in vivo oral delivery to obese mice.

Main Results:

• The SynIDP self-assembled into a functional enteric coating with tunable properties.
• The coating demonstrated reversible, intestinal cue-responsive phase transitions.
• Protected peptide drugs from simulated gastric conditions for over 60 minutes.
• Achieved more consistent weight loss in obese mice compared to unencapsulated drugs following oral administration.

Conclusions:

• Engineered SynIDPs provide a modular platform for advanced oral peptide drug delivery.
• The self-assembling enteric coating overcomes gastrointestinal barriers, enhancing drug stability and targeting.
• This technology holds promise for improving patient compliance and therapeutic outcomes for peptide-based treatments.