The Gastrointestinal Tract: A Unique Battlefield for Bioengineering Delivery Platforms

Traditional drug delivery methods for gastrointestinal diseases, including oral and systemic administration, often suffer from degradation, inadequate mucosal absorption, and off-target toxicity. Consequently, these methods result in low bioavailability and suboptimal therapeutic outcomes for localized conditions such as inflammation and early-stage cancer. This review examines the innovative integration of advanced bioengineering platforms with therapeutic gastrointestinal endoscopy to address these delivery challenges. We concentrate on three principal bioengineered platforms: (1) nanoparticle systems (e.g., lipid, polymeric, and inorganic nanoparticles) designed for localized chemotherapy and theranostics; (2) in situ-forming hydrogels that serve as intelligent wound management materials and sustained drug depots; and (3) drug-eluting and biodegradable stents that convert passive luminal scaffolds into active, long-term drug-releasing devices. An analysis of these platforms demonstrates that their synergy with endoscopy facilitates precise, minimally invasive, and sustained local therapy, potentially transforming the treatment landscape for gastrointestinal diseases such as cancer and inflammatory bowel disease. Additionally, we investigate advanced strategies, including active targeting and stimulus-responsive release mechanisms, to enhance spatial precision. Despite promising preclinical advancements, clinical translation encounters challenges related to long-term biocompatibility, scalable manufacturing, regulatory pathways for drug-device combinations, and cost-effectiveness. Ultimately, the convergence of bioengineering and endoscopy presents significant potential to usher in a new era of precise, localized, and sustained micro-invasive treatments in gastroenterology.