Enzymatic barriers for GI peptide and protein delivery

Area of Science:

• Pharmaceutical Science
• Drug Delivery
• Biochemistry

Background:

• Oral delivery of therapeutic peptides and proteins is hindered by the gastrointestinal (GI) tract's enzymatic degradation.
• The GI tract possesses numerous endo- and exopeptidases that break down peptides and proteins.

Purpose of the Study:

• To analyze the enzymatic barriers in the GI tract for oral peptide and protein delivery.
• To evaluate strategies for overcoming enzymatic degradation in oral peptide delivery.

Main Methods:

• Qualitative and quantitative analysis of peptidases in the small intestine lumen, brush border membrane, and colon.
• Review of existing and proposed strategies for oral peptide delivery.

Main Results:

• The small intestine lumen and brush border membrane present significant peptidase barriers.
• Microbial activity in the colon also contributes substantial peptidase activity.
• Enzyme inhibition and synthesis of enzyme-resistant peptide analogues are identified as key strategies.

Conclusions:

• Understanding the enzymatic barriers is crucial for designing effective oral peptide delivery systems.
• The synthesis of enzyme-resistant peptide analogues is the most promising approach for oral peptide delivery.