Oral delivery is considered the favoured route of administration for both local and systemic delivery of active molecules. Formulation of drugs in conventional systems and nanoparticles has provided opportunities for targeting the gastrointestinal (GI) tract, increasing drug solubility and bioavailability. Despite the achievements of these delivery approaches, the development of a product with the ability of delivering drug molecules at a specific site and according to patients’ needs remains a challenging endeavour. The complexity of the physicochemical properties of colloidal systems, their stability in different regions of the gastrointestinal tract, and interaction with the restrictive biological barriers hampered their success for oral precise medicine. To overcome these issues, nanoparticles have been combined with polymers to create hybrid nanosystems, namely nanocomposites. They offer enormous possibilities of structural and mechanical modifications to both nanoparticles and polymeric matrixes to generate systems with new properties, functions, and applications for oral delivery. In this review, nanocomposites’ physicochemical and functional properties intended to target specific regions of the GI tract—oral cavity, stomach, small bowel, and colon—are analysed. In parallel, it is provided an insight in the nanocomposite solutions for oral delivery intended for systemic and local absorption, together with a focus on inflammatory bowel diseases (IBDs). Additional difficulties in managing IBD related to the alteration in the physiology of the intestine are described. Finally, future perspectives and opportunities for advancement in this field are discussed.

Graphical abstract