Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System.

Area of Science:

• Biotechnology
• Nanotechnology
• Drug Delivery

Background:

• Thermostable exoshells (tES) are protein nanoparticles for encapsulating therapeutic proteins.
• Oral drug delivery is preferred but faces challenges with enzyme degradation in the digestive tract.

Purpose of the Study:

• To structurally enhance the stability of tES for oral drug delivery.
• To evaluate the protective capacity and intestinal permeability of modified tES.

Main Methods:

• Engineered tES with inter-subunit disulfide linkages (DS-tES).
• Assessed stability of encapsulated enzymes (horseradish peroxidase) against acidic pH and digestive enzymes (pepsin, trypsin).
• Evaluated intestinal permeability using Caco2 cell models and in vivo studies with encapsulated Renilla luciferase in mice.

Main Results:

• DS-tES significantly stabilized encapsulated enzymes compared to unmodified tES.
• DS-tES demonstrated enhanced intestinal permeability in vitro.
• In vivo studies showed ~3x greater enzyme stability and ~100x higher enzyme activity in feces after 24h oral administration compared to free enzyme.

Conclusions:

• Disulfide-linked thermostable exoshells (DS-tES) offer improved stability and permeability for oral drug delivery.
• DS-tES show potential for both intraluminal and systemic delivery of protein-based therapeutics.
• This nanoplatform represents a promising advancement in overcoming oral delivery barriers for sensitive biomolecules.