Intestinal retentive delivery system for improved disease therapy

Oral drug delivery systems (DDSs) show great advantages in patient compliance due to their convenience and non-invasiveness. Typically, oral DDSs are designed to deliver drugs to the specific gastrointestinal region, and normalize the dysregulated intestinal niche in situ, or facilitate their transport across the biological barriers including mucus and epithelial layers. Prolonging the residence time of oral DDSs in the gastrointestinal tract is indispensable in realizing these goals. However, the hostile gastric environment is not suitable for the retention of susceptible drugs. Intestinal retentive DDSs are promising alternatives for the oral delivery of these drugs. Moreover, intestinal retentive DDSs can provide opportunities for the regulation of mucosal immunity and gut microbiota. In this review, we briefly describe the general information of intestinal transit time and its influencing factors. We next summarize the recent advances of engineering strategies in prolonging the intestinal retention of oral DDSs at nano-, micro-, and macro-scales. While the underlying mechanisms of intestinal retention remain incompletely understood, we discuss the potential theories and evidence. In addition, we discuss how this prolonged retention of oral DDSs modulates the intestinal environment in situ and the systemic immunity.