Optimizing delivery to the gastrointestinal tract: a mechanistic approach to nutraceutical design and development

Nutraceuticals have garnered increasing scientific and commercial interest for their potential roles in health promotion, disease prevention and adjunctive disease management. However, the complex physicochemical and biological environment of the gastrointestinal (GI) tract presents formidable barriers to their effective oral delivery, contributing to a persistent gap between preclinical promise and clinical efficacy. A mechanistic understanding of GI physiology, nutraceutical-specific delivery challenges and available formulation strategies is therefore essential to advance the field.

Preclinical and clinical studies exploring the oral delivery of nutraceuticals were identified through targeted PubMed, Scopus and Web of Science searches to examine the GI tract as a dynamic delivery environment. Nutraceuticals are classified according to their primary delivery challenges, including lipophilicity, chemical and enzymatic lability and requirements for colon-targeted or microbiome-directed delivery. Formulation strategies are reviewed mechanistically, with particular attention to lipid-based systems, polymeric nanoparticles, hydrogel and hybrid biomaterials and colon-targeted delivery platforms.

Advancing nutraceutical science requires moving toward a formulation-driven approach to overcome the biological barriers faced by oral delivery. There is a critical need for regulatory oversight to ensure that marketed claims are backed by scientific evidence relating to nutraceutical pharmacokinetics, pharmacodynamics and safety evaluations.