Microenvironment-adaptive drug delivery systems for ulcerative colitis: from pathological constraints to rational design

INTRODUCTION: Ulcerative colitis (UC) is characterized by recurrent, chronic, and nonspecific intestinal inflammation. It is strongly associated with an increased risk of colorectal cancer, representing a global public health challenge. However, the complex pathological microenvironment of UC, characterized by mucus barrier disruption, increased epithelial permeability, immune dysregulation, and oxidative stress, substantially compromises the therapeutic efficacy of conventional drugs. AREAS COVERED: Nanomedicine delivery systems have offered new opportunities for UC treatment, these systems can optimize drug transport, distribution, and controlled release, thereby better addressing the therapeutic requirements of UC. Relevant literature was identified through PubMed, with a primary focus on studies published between January 2016 and August 2026. EXPERT OPINION: The fundamental relationship between disease pathology and delivery system design remains insufficiently explored. To address this gap, this review proposes a pathology-driven microenvironment-adaptive framework and critically evaluates the limitations of current delivery strategies. We translate the key pathological barriers into actionable design criteria, followed by a discussion of how molecular building blocks and delivery platforms can be engineered to realize microenvironment-adaptive therapeutic strategies. This review provides insights and new perspectives for the rational design of microenvironment-adaptive systems for UC.