Recent Progress in Chitosan Nanoparticles for the Oral Delivery of Proteins and Peptides: Strategies to Improve Bioavailability.

INTRODUCTION: The oral delivery of proteins or peptides remains a significant challenge due to enzymatic degradation in the gastrointestinal tract, low epithelial permeability, and low bioavailability. Chitosan nanoparticles (CNPs) have been developed to overcome these disadvantages due to their biodegradability, biocompatibility, mucoadhesiveness, and ability to transiently disrupt epithelial tight junctions, thereby improving drug absorption. METHODS: This review summarizes the latest literature from 2020 to 2025 on the physicochemical properties, formulations, preclinical and clinical studies, and regulatory issues related to CNP delivery systems. To ensure access to reliable peer-reviewed articles and scholarly sources, relevant studies were obtained from reputable scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. RESULTS: CNPs can effectively enhance the stability, absorption, and therapeutic efficacy of biopharmaceuticals. A number of studies reported encapsulation efficiencies as high as 90% and significant improvements in the oral bioavailability of insulin, anticancer drugs, and oral vaccines. Both in vitro and in vivo studies showed consistently better pharmacokinetic properties, increased mucosal permeation, and better therapeutic efficacy. Further, toxicological assessments showed good safety profiles at therapeutic doses. DISCUSSION: While there is significant potential, problems with scalability, stability, and regulatory standardization remain unresolved. New formulation technologies and individualised 'nanomedicine' could help to address these limitations. CONCLUSION: Overall, CNPs are a transformative nanoplatform with great potential to improve the delivery of biopharmaceuticals via the oral route, enhancing patient adherence and therapeutic efficacy.