Development of oral pH-sensitive redox nanotherapeutics for gastric ulcer therapy.

Autor: Tang MQ; School of Biomedical Engineering, International University, Ho Chi Minh 700000, Viet Nam; Vietnam National University Ho Chi Minh City (VNU-HCM), Ho Chi Minh 700000, Viet Nam., Tran NB; School of Biomedical Engineering, International University, Ho Chi Minh 700000, Viet Nam; Vietnam National University Ho Chi Minh City (VNU-HCM), Ho Chi Minh 700000, Viet Nam., Nguyen TT; School of Biomedical Engineering, International University, Ho Chi Minh 700000, Viet Nam; Vietnam National University Ho Chi Minh City (VNU-HCM), Ho Chi Minh 700000, Viet Nam., Nguyen KH; Vietnam National University Ho Chi Minh City (VNU-HCM), Ho Chi Minh 700000, Viet Nam; Faculty of Biology and Biotechnology, University of Science Ho Chi Minh 700000, Viet Nam., Trinh NT; School of Biomedical Engineering, International University, Ho Chi Minh 700000, Viet Nam; Vietnam National University Ho Chi Minh City (VNU-HCM), Ho Chi Minh 700000, Viet Nam., Van Vo T; School of Biomedical Engineering, International University, Ho Chi Minh 700000, Viet Nam; Vietnam National University Ho Chi Minh City (VNU-HCM), Ho Chi Minh 700000, Viet Nam., Kobayashi M; Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan., Yoshitomi T; Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan., Nagasaki Y; Department of Materials Science, Faculty of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Center for Research in Radiation and Earth System Science (CRiES), University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8654, Japan; High-Value Biomaterials Research and Commercialization Center (HBRCC), National Taipei University of Technology, Taipei 10608, Taiwan. Electronic address: happyhusband@nagalabo.jp., Vong LB; School of Biomedical Engineering, International University, Ho Chi Minh 700000, Viet Nam; Vietnam National University Ho Chi Minh City (VNU-HCM), Ho Chi Minh 700000, Viet Nam. Electronic address: vblong@hcmiu.edu.vn.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Nov; Vol. 375, pp. 758-766. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1016/j.jconrel.2024.09.039
Abstrakt: Gastric ulcer is a common gastrointestinal disorder worldwide. Although its pathogenesis is unclear, the overproduction of reactive oxygen species (ROS), which results in an oxidative imbalance, has been reported as a central driving mechanism. Within the scope of this investigation, we developed two different self-assembling redox nanoparticles (RNPs) with ROS-scavenging features for the oral treatment of gastric ulcers. One of them, referred to as RNP N , disintegrates in response to acidic pH, whereas the other, denoted as RNP O , remains intact regardless of pH variations. Both types of RNPs showed different free radical scavenging activities in vitro. Protonation of the amino linkages in the side chains of RNP N caused the micelle structure to collapse and the nitroxide radicals encapsulated in the core were exposed to the outside, resulting in a significant increase in antioxidant capacity as the pH decreases. In contrast, RNP O maintained its spherical structure and consistent antioxidant reactivity irrespective of pH changes. The in vivo gastric retention of orally administered RNP N was significantly improved compared to that of RNP O which might be explained by the increased exposure of cationic protonating segments in RNP N on the negatively charged gastric mucosal surface. Owing to its improved gastric retention and enhanced ROS scavenging capacity under acidic pH conditions, RNP N exhibited superior protective effects against oxidative stress induced by aspirin in a gastric ulcer mouse model compared to RNP O . In addition, neither RNP N nor RNP O resulted in severe lethal effects or significant changes in the morphology of zebrafish embryos, indicating their biosafety. Our results suggest that the oral administration of RNPs has a high therapeutic potential for gastric ulcer treatment.
Competing Interests: Declaration of competing interest The University of Tsukuba has a patent for the material developed in this study, licensed to CrestecBio.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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