Emerging trends in permeation-enhancing technologies for oral peptide delivery

Peptides are increasingly favored as therapeutic agents due to their high efficacy, selectivity, and minimal side effects. However, they often face challenges related to poor stability and limited permeability through the gastrointestinal tract (GIT) and epithelia, necessitating parenteral administration. Despite this, there is a considerable demand for oral administration in clinical practice. To address the urgent clinical need for oral delivery, researchers have developed various technologies to surmount these challenges, including device-related systems, permeation enhancers (PEs), nanocarrier-based systems, and more. This review systematically explores the physiological barriers impacting peptide permeability and discusses the permeation-enhancing technologies designed to overcome them. It also reviews the oral peptide delivery systems currently available or under clinical investigation, offering insights into future developments in this field. This review comprehensively analyzes the physiological barriers that impact peptide permeability and evaluates the various permeation-enhancing technologies designed to overcome them. Additionally, it summarizes current advancements in oral peptide delivery systems, offering insights into potential future directions and innovations in this field.