Specific accumulation of orally administered redox nanotherapeutics in the inflamed colon reducing inflammation with dose-response efficacy.

Abstract

Although current medications for ulcerative colitis (UC) are effective to some extent, there are still some limitation of their use due to the non-specific distribution, drug metabolism in the gastrointestinal tract, and severe adverse effects. In our previous studies, we developed oral redox nanoparticles (RNP(O)) that specifically accumulated and scavenged overproduced reactive oxygen species (ROS) in an inflamed colon. However, the mechanism leading to specific accumulation of RNP(O) in an inflamed colon is still unclear. In this study, we investigated the cellular uptake of RNP(O) into ROS-treated epithelial colonic cells in vitro, and compared to the untreated cells, found a significantly increased uptake in ROS-treated cells. In vivo, we discovered that orally administered RNP(O) were not internalized into the cells of a normal colon. A significant amount of disintegrated RNP(O) was detected in the cells of an inflamed colon of dextran sodium sulfate (DSS)-induced colitis mice, resulting in scavenging of ROS and suppression of inflammation with low adverse effects. Furthermore, we confirmed a significant reduction of disease activity and a robust dose response efficacy following RNP(O) treatment in acute DSS-induced colitis mice, outperforming the positive control 5-aminosalicylic acid. Oral administration of RNP(O) is a promising approach to develop a new therapy for UC disease.

• Authors: Long Binh Vong, John Mo, Bertil Abrahamsson, Yukio Nagasaki
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 210 Pg. 19-25 (Jul 28 2015) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 25998050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Interleukin-8
• Leukocyte L1 Antigen Complex
• Oxidants
• Dextran Sulfate
• Hydrogen Peroxide

Topics

• Administration, Oral
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Caco-2 Cells
• Colitis, Ulcerative (chemically induced, drug therapy, metabolism, pathology)
• Colon (drug effects, pathology)
• Dextran Sulfate
• Dose-Response Relationship, Drug
• Humans
• Hydrogen Peroxide (pharmacology)
• Interleukin-8 (metabolism)
• Leukocyte L1 Antigen Complex (metabolism)
• Male
• Mice
• Mice, Inbred ICR
• Nanoparticles (therapeutic use)
• Oxidants (pharmacology)
• Oxidation-Reduction