Oral delivery of protein and peptide therapeutics.

Abstract

Oral administration of proteins and peptides has gained significant attention recently due to its potential to transform therapeutic strategies, providing a non-invasive and patient-friendly method for delivering biopharmaceuticals. The primary hurdle in oral delivery stems from the harsh conditions of the gastrointestinal (GI) tract, characterized by acidic pH, enzymatic degradation, and limited permeability across the intestinal epithelium. Various innovative approaches have emerged to overcome these challenges, including nanoparticle-based delivery systems, mucoadhesive formulations, and chemical modifications of peptides aimed at improving stability and absorption rates. Nanoparticle-based delivery systems, such as liposomes, polymeric nanoparticles, and solid lipid nanoparticles, hold promise in protecting proteins and peptides from enzymatic degradation while enhancing their bioavailability. These nanoparticles can be tailored to target specific areas within the GI tract, extending drug release and enhancing therapeutic effectiveness. Mucoadhesive formulations utilize polymers like chitosan, alginate, and polyethylene glycol (PEG) derivatives to adhere to GI mucosal surfaces, prolonging residence time and facilitating drug absorption. Chemical modifications, such as PEGylation, glycosylation, and lipidation have been employed to enhance the stability and permeability of proteins and peptides in the GI tract. PEGylation, in particular, has been widely used to extend the circulation half-life and reduce the immunogenicity of therapeutic proteins. Advancements in nanotechnology, especially the development of smart nanocarriers capable of responsive drug release triggered by pH or enzymatic stimuli, show promise in further improving oral delivery of proteins and peptides. The integration of bioinformatics and computational modeling techniques has facilitated the design of novel drug delivery systems with optimized pharmacokinetic profiles. This chapter focuses on the advancements and challenges in the oral delivery of protein and peptide-based drugs, highlighting the innovative strategies being explored to enhance therapeutic outcomes.