Smart intraoral systems for advanced drug delivery

Drug administration through the oral cavity is considered to be a convenient, effective, and time-saving strategy in the clinic with high safety and quick onset, especially for patients with needle fear and swallowing difficulties. Without the degradation in gastrointestinal tract and first-pass metabolism, the intraoral drug delivery system turns out to be an attractive option for macromolecule absorption, which will provide a promising platform for the successful delivery of protein, peptide, nucleic acid, and polysaccharide. Nevertheless, limited bioavailability, short retention time, and poor reproducibility pose a major hurdle to the further application of conventional intraoral drug delivery systems. Recent advances in chemical, material, and engineering techniques bring great opportunities to improve intraoral system fabrication and applications, owing to the high biocompatibility and functional diversity. In this review, we systematically summarize the recent development of smart intraoral drug delivery systems, including fast dissolving oral films, medicinal chewing gum systems, intraoral mucoadhesive systems, physical assisted systems, intelligent intraoral device, and chemically assisted systems. Moreover, the challenges and prospects for clinical and industrial applications of current strategies are well discussed. It is believed that the smart intraoral system would serve as a promising candidate to improve human life in the near future.