Bioactive Peptide Bioavailability: Review Uncovers Barriers, Transport, and Enhancement Strategies

Despite their high target specificity and potent bioactivity, bioactive peptides (BAPs) face significant hurdles in clinical application due to poor bioavailability. This limitation primarily stems from biochemical barriers like gastric acid and digestive enzyme degradation, coupled with the intricate physical barriers of the intestinal epithelium. Intrinsic physicochemical properties, such as molecular size and hydrophobicity, further complicate their journey in vivo. A thorough understanding of their absorption kinetics and transport pathways is crucial to unlock the full therapeutic potential of these multifunctional molecules, which exhibit antioxidant, antihypertensive, immunomodulatory, hypoglycemic, and antitumor activities.

This systematic review comprehensively examined the multifaceted barrier mechanisms that impede peptide digestion and absorption in vivo. Researchers elucidated the complex physiological processes involved in in vivo transport pathways of bioactive peptides. Furthermore, the review proposed and analyzed cutting-edge strategies specifically designed to enhance peptide bioavailability. The work synthesized current knowledge to establish a theoretical framework and practical guidance for optimizing peptide absorption and delivery, aiming to facilitate their broader clinical applications.

The review systematically identified key barriers to bioactive peptide bioavailability, including rapid degradation by gastric acid and various digestive enzymes, alongside the formidable multilayer physical barriers of the intestinal epithelium. It detailed how intrinsic physicochemical properties, such as molecular size and hydrophobicity, significantly influence peptide absorption. The authors elucidated sophisticated in vivo transport mechanisms, highlighting the intricate physiological processes involved in peptide movement across biological membranes.

The review provides a comprehensive theoretical framework and practical guidance for optimizing peptide absorption and delivery, emphasizing the critical need to overcome these barriers for successful therapeutic translation. It also presented advanced strategies to circumvent these challenges, paving the way for more efficacious peptide-based therapeutics by improving their systemic exposure and target site delivery.