Advances of oral micro- and nanomedicines for modulating intestinal barriers in the treatment of intestinal diseases.

The oral delivery of drugs for treating intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), is hindered by four primary intestinal barriers: chemical, microbial, mechanical, and immunological barriers. Micro- and nanoparticles have garnered significant attention as platforms for intestinal-targeted delivery due to their small size and unique structural composition, which enhance drug accumulation and prolong residence time at the site of action, thereby facilitating localized therapy. Oral micro/nanomedicines have emerged as a promising strategy to overcome these barriers and enable the selective targeting of drugs to pathological sites within the intestine. This review systematically examines the chemical, microbial, mechanical, and immune barriers of the intestinal mucosa encountered in intestinal diseases, introduces oral micro/nanomedicines designed to target these barriers, discusses their latest advancements in the context of intestinal diseases, and ultimately provides insights into the challenges faced by oral micro/nanomedicine.