Orally Administered Nanoparticle Coacervate for Therapeutic Coating of Full Gastrointestinal Tract

Oral delivery of therapeutic nanoparticles offers a non-invasive approach for treating gastrointestinal diseases, but achieving localized and sustained mucosal exposure while avoiding systemic toxicity remains a major challenge. Here, a Sucralfate-based oral formulation is developed that incorporates therapeutic nanoparticles and transforms into a paste-like coacervate upon contact with intestinal fluid, uniformly coating the entire gastrointestinal tract within 6 h, and clearing through fecal transit by 12 h. Systematic investigation shows that nanoparticle hydrophobicity is essential for stable incorporation into Sucralfate-based formulation, supporting compatibility with a wide range of nanoparticle types. The incorporated nanoparticles are stabilized by strong non-covalent interactions, which limit gastric leaching and reduce cellular uptake by 0.044% compared with PEGylated nanopart…