The Role of Chitosan-Based Nanoparticles in Enhancing the Oral Bioavailability of Protein and Peptide Drugs

Abstract

Insulin, calcitonin, growth hormone, and other peptide-based drugs are currently administered predominantly by injection, since, when taken orally, they lose almost all of their activity owing to the acidic environment of the gastrointestinal tract, proteolytic enzymes, and the epithelial barrier — the absolute oral bioavailability of such preparations is typically below 1%. Chitosan — a natural, biosensitive, and minimally toxic polysaccharide — is being extensively studied as a promising platform for the oral delivery of peptide drugs owing to its cationic nature, mucoadhesive properties, and its ability to transiently open the tight junctions between epithelial cells. This article analyzes the mechanisms by which chitosan nanoparticles protect peptide drugs from enzymatic degradation, adhere to the mucosal layer (mucoadhesion), and enhance absorption via paracellular transport, and it further examines the comparative efficacy of pH-sensitive and ligand-modified chitosan systems. Research on chitosan derivatives conducted at the Institute of Polymer Chemistry and Physics of the Academy of Sciences of the Republic of Uzbekistan is discussed within the national context.