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説明:

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 RNPN, disintegrates in response to acidic pH, whereas the other, denoted as RNPO, 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 RNPN 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, RNPO maintained its spherical structure and consistent antioxidant reactivity irrespective of pH changes. The in vivo gastric retention of orally administered RNPN was significantly improved compared to that of RNPO which might be explained by the increased exposure of cationic protonating segments in RNPN on the negatively charged gastric mucosal surface. Owing to its improved gastric retention and enhanced ROS scavenging capacity under acidic pH conditions, RNPN exhibited superior protective effects against oxidative stress induced by aspirin in a gastric ulcer mouse model compared to RNPO. In addition, neither RNPN nor RNPO 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.

権利情報:

• Creative Commons BY-NC-ND Attribution-NonCommercial-NoDerivs 4.0 International
  © 2024. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/

キーワード: ROS , Redox nanoparticles , pH-sensitive , Oral delivery , Aspirin , Gastric ulcer

刊行年月日: 2024-10-01

出版者: Elsevier BV

掲載誌:

• Journal of Controlled Release (ISSN: 01683659) vol. 375 p. 758-766

研究助成金:

• Foundation for Promotion of Material Science and Technology of Japan

原稿種別: 著者最終稿 (Accepted manuscript)

MDR DOI: https://doi.org/10.48505/nims.5071

公開URL: https://doi.org/10.1016/j.jconrel.2024.09.039

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更新時刻: 2025-10-02 08:30:21 +0900

MDRでの公開時刻: 2025-10-02 08:18:52 +0900