Oral Peptide Delivery Systems: Synergistic Approaches Using Polymers, Lipids, Nanotechnology, and Needle-Based Carriers

Oral peptide delivery remains a significant challenge due to physiological barriers, enzymatic degradation, and limited permeability in the gastrointestinal tract (GIT). The harsh conditions of the GIT, including enzymatic hydrolysis and pH variations, contribute to the instability of peptides, leading to poor bioavailability. To overcome these challenges, advanced drug delivery systems have been developed, incorporating various strategies to enhance peptide absorption. These include polymer-based carriers that can enhance mucoadhesion or mucodiffusion, bacteria-based systems that facilitate binding, and a range of nanoparticle systems—such as lipid- and polymer-based carriers—that protect peptides from enzymatic degradation. Additionally, chemical and structural modifications, as well as targeting ligands, have been explored to enhance stability and absorption. Recent innovations in oral peptide drug delivery include novel formulations such as Eligen and ORLADEL oral tablets, insulin bubble carriers, and intestinal patches. The use of mesoporous carriers has also gained attention for their ability to improve peptide stability and permeability. Furthermore, swallowable needle-based systems such as LUMI and SOMA have been developed to facilitate insulin delivery. These advancements represent promising solutions for improving oral peptide bioavailability, yet further research is needed to refine these technologies and ensure their safety, scalability, and efficacy in clinical applications.