Bio-inspired helical microcarriers anchoring quercetin nanoparticles enable prolonged and self-trackable colonic delivery in colitis

Abstract

Oral antioxidant therapy for Inflammatory Bowel Disease (IBD) is currently hampered by the “oral delivery paradox”, wherein the therapeutic potential of bioactive agents is compromised by poor aqueous solubility and rapid gastrointestinal washout. To overcome these biopharmaceutical barriers, we engineered a bio-inspired theranostic platform (QUE@SP) via the electrostatic anchoring of cationic, quercetin-loaded zein/chitosan nanoparticles onto the surface of the natural helical microcarrier, Spirulina platensis (SP). Mechanistically, the biomimetic helical morphology of SP induces a hydrodynamic locking effect within the intestinal villi, transforming the transient transit of nanoparticles into a sustained mucosal depot. Following mucosal attachment, the controlled release of quercetin is driven by microbiota-triggered enzymatic degradation of the chitosan-zein matrix, ensuring site-specific drug discharge. In vivo evaluations demonstrated a prolonged colonic retention of up to 48 hours, which maximized localized drug exposure. This translated into potent reactive oxygen species (ROS) scavenging, macrophage polarization, and the restoration of intestinal barrier integrity in colitis murine models. Furthermore, as an inherently biocompatible carrier, SP facilitated self-trackable monitoring of mucosal distribution via its intrinsic fluorescence, followed by complete biodegradation and nutritional absorption. Ultimately, this work introduces a shape-driven paradigm that repurposes natural microalgae into a precision oral vehicle, providing a biologically integrated strategy for targeted colitis therapy.