Enhancing Oral Bioavailability of Therapeutic Peptides Using Permeation Enhancer and Nanocarrier Hybrid Systems
Keywords:
Therapeutic Peptides; Oral Bioavailability; Permeation Enhancers; Nanocarriers; Hybrid Delivery Systems; Intestinal BarrierAbstract
Therapeutic peptides have emerged as promising candidates for treating a wide range of diseases, including metabolic disorders, cancers, and autoimmune conditions, owing to their high specificity, potency, and low toxicity. However, their oral administration remains a major challenge because of their poor bioavailability, primarily due to gastrointestinal (GI) enzymatic degradation, low intestinal epithelial permeability, and first-pass metabolism. Conventional delivery systems often fail to overcome these barriers, limiting the clinical application of oral peptide formulations in humans. In recent years, permeation enhancer and nanocarrier hybrid systems have gained significant attention as an innovative strategy to overcome these limitations. By integrating the advantages of permeation enhancers (which modulate intestinal barrier function) and nanocarriers (which protect peptides from degradation and improve targeted delivery), these hybrid systems can synergistically enhance the oral bioavailability of therapeutic peptides. This review summarises the key challenges in oral peptide delivery, elaborates on the mechanisms of action of permeation enhancers and nanocarriers, and highlights the design, optimisation, and in vitro and in vivo performance of hybrid systems. In addition, current advancements, clinical translation prospects, and future directions in this field are discussed to provide insights into the development of effective oral peptide formulations.
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