Oral peptide delivery: Translational challenges due to physiological effects

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Biotechnology

Background:

• Oral peptide delivery offers a convenient alternative to injections but faces significant hurdles.
• Low pH, enzymatic degradation, and poor absorption limit peptide bioavailability and cause high inter-subject variability.
• Existing research lacks a systematic analysis of physiological barriers hindering clinical translation.

Purpose of the Study:

• To analyze the physiological barriers within the gastrointestinal (GI) tract responsible for low bioavailability and high variability of oral peptide delivery.
• To identify key factors influencing oral peptide absorption, including GI tract parameters, pH, food effects, and peptidases.
• To highlight impediments in current research, such as lack of in vitro-in vivo correlations and animal model variability.

Main Methods:

• Analysis of physiological barriers in the gastrointestinal tract.
• Detailed examination of GI tract parameters influencing peptide uptake.
• Review of factors like pH, food effect, and peptidases on oral peptide absorption.

Main Results:

• Identified low pH, enzymatic instability, and tight junction transport as primary barriers to oral peptide absorption.
• Highlighted the significant impact of GI tract parameters, including pH and food, on peptide bioavailability.
• Noted variability in animal models and lack of in vitro-in vivo correlations as key challenges.

Conclusions:

• Understanding GI physiological barriers is crucial for developing successful oral peptide therapeutics.
• Addressing these barriers can lead to improved developability and clinical translation of oral peptide drugs.
• This analysis provides a foundation for future research in personalized, patient-centric oral biologic therapies.