Abstract

Bioactive peptides and proteins can be administered orally. However, this method remains largely ineffective because of enzymatic degradation in the gastrointestinal tract, the mucus layer, the selective epithelial barrier, the acidic stomach environment, and a short half-life. As a result, bioactive protein molecules have little prospect as functional food ingredients unless appropriate delivery systems are used. This review describes scientific trends and strategies aimed at solving the problem of the instability of peptides and proteins in the gastrointestinal tract during oral administration.
The review analyzed scientific publications on the oral administration, stability, and bioavailability of peptides and proteins in the gastrointestinal tract registered in eLIBRARY.RU, MEDLINE, PubMed, EMBASE, Scopus, Web of Science, and Google Scholar between 2020 and 2025 (alongside some fundamental earlier works). Of the 1,346 manually selected publications, the review included 116 articles.
Peptides can be encapsulated in solid lipid nanoparticles, nanostructured lipid carriers, liposomes, or polymer nanocarriers. Encapsulation increases stability and bioavailability during oral administration. Cell-penetrating peptides and their integration with various drug carriers create multifunctional delivery systems. Modified living biotherapeutic products are promising carriers for the targeted delivery of peptides and proteins. Novel methods include matrix protein amplification, protease inhibitors, permeability enhancers, chemical modification, and cyclization.
The article also describes new cyclic biopeptides, a recombinant protein, and a native antiviral peptide with reliable bioactive properties. The maltodextrin-encapsulated antiviral peptide demonstrated a 1.8-fold increase in intestinal stability in vitro.

Keywords

Peptides, proteins, oral delivery, cell-penetrating peptides, advanced microbial therapy, permeability enhancers, polymer systems, encapsulation, lipid carriers

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