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Lipid nanoparticle (LNP)-based drug delivery systems (DDSs) are widely recognized for their ability to enhance efficient and precise delivery of therapeutic agents, including nucleic acids like DNA and mRNA. Despite this acknowledgment, there is a notable knowledge gap regarding the systemic biodistribution and organ accumulation of these nanoparticles. The ability to track LNPs in vivo is crucial for understanding their fate within biological systems. Fluorescent labeling of LNPs facilitates real-time tracking, quantification, and visualization of their behavior within biological systems, providing valuable insights into biodistribution, cellular uptake, and the optimization of drug delivery strategies. Our prior research established reversely engineered LNPs as an exceptional mRNA delivery platform for treating ulcerative colitis. This study presents a detailed protocol for labeling interleukin-22 (IL-22) mRNA-loaded LNPs, their oral administration to mice, and visualization of DiR-labeled LNPs biodistribution in the gastrointestinal tract using IVIS spectrum. This fluorescence-based approach will assist researchers in gaining a dynamic understanding of nanoparticle fate in other models of interest.

Inflammatory bowel disease (IBD), marked by chronic gastrointestinal tract inflammation, poses a significant global medical challenge. Current treatments for IBD, including corticosteroids, immunomodulators, and biologics, often require frequent systemic administration through parenteral delivery, leading to nonspecific drug distribution, suboptimal therapeutic outcomes, and adverse effects. There is a pressing need for a targeted drug delivery system to enhance drug efficacy and minimize its systemic impact. Nanotechnology emerges as a transformative solution, enabling precise oral drug delivery to inflamed intestinal tissues, reducing off-target effects, and enhancing therapeutic efficiency. The advantages include heightened bioavailability, sustained drug release, and improved cellular uptake. Additionally, the nano-based approach allows for the integration of theranostic elements, enabling simultaneous diagnosis and treatment. Recent preclinical advances in oral IBD treatments, particularly with nanoformulations such as functionalized polymeric and lipid nanoparticles, demonstrate remarkable cell-targeting ability and biosafety, promising to overcome the limitations of conventional therapies. These developments signify a paradigm shift toward personalized and effective oral IBD management. This review explores the potential of oral nanomedicine to enhance IBD treatment significantly, focusing specifically on cell-targeting oral drug delivery system for potential use in IBD management. We also examine emerging technologies such as theranostic nanoparticles and artificial intelligence, identifying avenues for the practical translation of nanomedicines into clinical applications.