Orally Administered Nanoparticle Coacervate for Therapeutic Coating of Full Gastrointestinal Tract
Abstract
ABSTRACT 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 nanoparticles. As a representative example, antioxidant cerium oxide nanoparticles are tested in two distinct oxidative stress‐related models of intestinal injury, including immune‐mediated colitis and radiation‐induced enteropathy. In DSS colitis, our system reduced weight loss from 17.2% to 2.2% and restored colon structure and oxidative‐stress injury. In radiation‐induced enteropathy, our system attenuated weight loss from 25.5% to 11.4%, doubled villus length, and markedly enhanced epithelial regeneration. The formulation also accommodates nanoparticles with imaging capability, demonstrating versatility for both therapeutic and diagnostic applications in gastrointestinal diseases.
Article Details
Authors (22)
Yunjung Lee
Center For Nanoparticle Research Institute for Basic Science (IBS) Seoul Republic of Korea
Youngjoon Kim
Department of Physiology School of Dentistry and Dental Research Institute Seoul National University Seoul Republic of Korea
Seokjun Kwon
Department of Physiology School of Dentistry and Dental Research Institute Seoul National University Seoul Republic of Korea
Ok Kyu Park
Center For Nanoparticle Research Institute for Basic Science (IBS) Seoul Republic of Korea
Gyeong Ho Min
Center For Nanoparticle Research Institute for Basic Science (IBS) Seoul Republic of Korea
Jinyoung Chu
Center For Nanoparticle Research Institute for Basic Science (IBS) Seoul Republic of Korea
Yubeen Kim
Center For Nanoparticle Research Institute for Basic Science (IBS) Seoul Republic of Korea
Johyun Yoon
Center For Nanoparticle Research Institute for Basic Science (IBS) Seoul Republic of Korea
Hyochul Lee
Department of Radiology Seoul National University College of Medicine Seoul Republic of Korea
Hojun Kim
Min Soh
Center for Advanced Pharmaceutical Technology HTnB Inc Seoul Republic of Korea
Nohyun Lee
School of Advanced Materials Engineering Kookmin University Seoul Republic of Korea
Hojeong Jeon
Biomaterials Research Center Biomedical Research Division Korea Institute of Science and Technology Seoul Republic of Korea
Yu‐Chan Kim
Biomaterials Research Center Biomedical Research Division Korea Institute of Science and Technology Seoul Republic of Korea
Junchul Kim
Department of Physiology School of Dentistry and Dental Research Institute Seoul National University Seoul Republic of Korea
Ki Baek Yeo
Institute for Clinical Dental Science Korea University Medical Center Seoul Republic of Korea
Seung Hong Choi
Sang Ho Jun
Department of Oral and Maxillofacial Surgery Korea University Anam Hospital Seoul Republic of Korea
Yuhan Lee
Department of Anesthesiology Perioperative and Pain Medicine Center for Accelerated Medicine Innovation and Center for Nanomedicine Brigham and Women's Hospital Harvard Medical School Massachusetts USA
Taeghwan Hyeon
Center for Nanoparticle Research
Sang‐woo Lee
Center For Nanoparticle Research Institute for Basic Science (IBS) Seoul Republic of Korea
Sang Ihn Han
Center For Nanoparticle Research Institute for Basic Science (IBS) Seoul Republic of Korea