Targeting IBD treatment: smart drug delivery systems for oral administration

Inflammatory bowel disease is a global widespread condition that significantly reduces patients' quality of life. Conventional oral therapies suffer from poor site-specific targeting, systemic absorption, and limited drug stability, leading to reduced efficacy and adverse effects. Smart drug delivery systems have emerged as a promising strategy to overcome these challenges by leveraging stimuli-responsive mechanisms, including internal triggers (pH, reactive oxygen species, enzymes, receptors and microbiota) and external stimuli (magnetic fields, light, ultrasound and temperature). These advanced platforms enable precise, localized drug release, enhancing therapeutic efficacy, minimizing systemic toxicity, and improving patient compliance. Preclinical studies highlight their potential in prolonging remission and promoting mucosal healing. As research progresses, further optimization of formulation design, clinical validation, and addressing interpatient variability will be essential for translating these innovative drug delivery systems into effective clinical applications for IBD management. Herein, we summarize and discuss the rational design of smart oral drug delivery systems for IBD treatment, highlighting their mechanisms, therapeutic advantages, and current challenges. The potential clinical applications, along with existing limitations and future directions for optimizing these advanced delivery platforms, are also clarified.