Polysaccharide-Based Nanocarriers for Oral Delivery of Proteins and Peptides: A Paradigm Shift in Biopharmaceutical Transport

Abstract

The oral administration of protein and peptide drugs (PPDs) remains a significant challenge due to the harsh physiological environment of the gastrointestinal (GI) tract. PPDs are susceptible to enzymatic degradation, denaturation from pH extremes, and poor absorption across the intestinal epithelium. To overcome these barriers, polysaccharide-based nanocarriers have emerged as a highly promising delivery platform. This manuscript provides a comprehensive overview of the design, fabrication, and application of these nanocarriers, using insulin as a model drug. The review highlights the unique properties of key polysaccharides like chitosan and alginate, which enable pH-responsive drug release and enhance intestinal permeability through mucoadhesion and tight junction modulation. The methodology section details fabrication techniques such as ionic gelation and polyelectrolyte complexation, alongside characterization methods and both in vitro and in vivo studies to evaluate efficacy. Results from such studies demonstrate that these nanocarriers successfully protect PPDs from degradation, leading to a significant increase in oral bioavailability. While challenges related to batch-to-batch reproducibility and clinical scalability remain, the use of biocompatible and biodegradable polysaccharides holds immense potential for developing patient-friendly oral formulations for PPDs.