Nanoparticle-assembled bioadhesive coacervate coating with prolonged gastrointestinal retention for inflammatory bowel disease therapy

• Published in: Nature communications Vol. 12; no. 1; pp. 7162 - 13
• Main Authors: Zhao, Pengchao, Xia, Xianfeng, Xu, Xiayi, Leung, Kevin Kai Chung, Rai, Aliza, Deng, Yingrui, Yang, Boguang, Lai, Huasheng, Peng, Xin, Shi, Peng, Zhang, Honglu, Chiu, Philip Wai Yan, Bian, Liming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.12.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/51; 14; 14/19; 14/34; 147/143; 38/77; 59; 631/154/152; 631/61/54/990; 639/301/54/990; 639/638/541/966; 64/86; 692/699/1503/257/1389; Administration, Oral; Animals; Coating; Coatings; Colitis; Controlled release; Drug carriers; Drug Carriers - chemistry; Drug delivery; Drug delivery systems; Drug Delivery Systems - instrumentation; Drug Delivery Systems - methods; Electrostatic properties; Female; Gastrointestinal diseases; Gastrointestinal system; Gastrointestinal tract; Gastrointestinal Tract - drug effects; Health services; Humanities and Social Sciences; Humans; Hydrogen bonding; Hydrogen-Ion Concentration; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Intestinal microflora; Intestine; Microbiota; multidisciplinary; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Oral administration; Rats; Rats, Sprague-Dawley; Residence time distribution; Retention; Science; Science (multidisciplinary); Signs and symptoms; Static Electricity; Structural stability; Sustained release
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27463-6

A key challenge for the effective treatment of gastrointestinal diseases including inflammatory bowel disease is to develop an orally administered drug delivery system capable of prolonged retention in the gastrointestinal tract. Herein we report a bioadhesive liquid coacervate based on hydrogen bonding-driven nanoparticle assembly. Free from electrostatic interactions, our fluid nanoparticle-assembled coacervate demonstrates significant pH- and salt-independent structural stability and forms a physically adhesive coating on a large surface area of intestinal tract with an extended residence time of more than 2 days to mediate the sustained release of preloaded water-soluble small molecule drugs in vivo. The orally administered drug-laden nanoparticle-assembled coacervate significantly mitigates the symptoms of inflammatory bowel disease, restores the diversity of gut microbiota, reduces systemic drug exposure, and improves the therapeutic efficacy in a rat acute colitis model compared with the oral administration of the same amount of drug in solution form. We suggest that the nanoparticle-assembled coacervate provides a promising drug delivery platform for management and treatment of numerous gastrointestinal diseases where controlled drug release with extended residence time is desired. The development of a drug delivery system capable of prolonged retention in the gastrointestinal tract remains a clinical challenge. Here the authors present a bio-adhesive liquid coacervate coating on the intestinal tract that acts as a flowable drug carrier, mediates the sustained release of diverse drugs, and potentially enhances therapeutic efficacy against gastrointestinal diseases.