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用于口服给药的磁性可导航丝素蛋白微针:确保在胃中持久根除幽门螺杆菌并快速止血。

Magnetic-navigable silk fibroin microneedles for oral drug delivery: Ensuring long-lasting helicobacter pylori eradication and rapid hemostasis in the stomach.

作者信息

Qiu Haoyu, Gong Lisha, Slezak Paul, He Shixiong, Lu Fei, Yu Kun, Xie Jing, Geng Zhen, Hu Enling, Zhou Zhihang, Lan Guangqian, Xie Ruiqi

机构信息

State Key Laboratory of Resource Insects, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China.

Ludwig Boltzmann Institute for Traumatology, AUVA Research Center, Vienna 1200, Austria.

出版信息

Int J Biol Macromol. 2024 Aug;275(Pt 1):133584. doi: 10.1016/j.ijbiomac.2024.133584. Epub 2024 Jul 1.

DOI:10.1016/j.ijbiomac.2024.133584
PMID:38960271
Abstract

The Helicobacter pylori infection in the stomach is the key reason for gastric mucosal bleeding. Eliminating gastric Helicobacter pylori by oral treatment remains difficult due to the presence of the gastric mucosal layer, which acts as a physical barrier to drugs via oral administration. In this study, a magnetic-navigable microneedle drug delivery platform (MNsD) for oral administration, featuring differential dual-mode drug release rate, was designed to fulfil rapid gastric hemostasis and overcome the gastric barriers for long-lasting Helicobacter pylori inhibition in stomach. MNs-D was created by rationally loading the carrier substrate, which was composed of silk fibroin with variable solubility, with antibiotics and hemostats. In vitro experiments showed MNs-D may sustainably eradicate Helicobacter pylori in stimulated gastric juices with long-lasting drug release (79 % in 24 h) and quickly establish hemostasis with instant drug release (92 % within 60 s). Most importantly, in vivo studies demonstrated MNs-D overcame the unsettling gastric mucosal barrier in traditional therapies of oral administration by insertion into the GML under magnetic navigation, resulting in sustained antibiotic release for long-lasting Helicobacter pylori eradiation (99 %). For differential dual-mode medication release against gastric Helicobacter pylori infections, this study may have firstly examined the effects of magnetic navigated microneedles administered orally.

摘要

胃内幽门螺杆菌感染是胃黏膜出血的关键原因。由于胃黏膜层的存在,通过口服治疗消除胃内幽门螺杆菌仍然很困难,胃黏膜层对口服药物起到了物理屏障的作用。在本研究中,设计了一种用于口服给药的磁导航微针给药平台(MNsD),其具有不同的双模式药物释放速率,旨在实现快速胃止血,并克服胃屏障以长期抑制胃内幽门螺杆菌。MNs-D是通过合理地将由不同溶解度的丝素蛋白组成的载体基质与抗生素和止血剂负载在一起而制成的。体外实验表明,MNs-D可以在模拟胃液中持续根除幽门螺杆菌,药物释放持久(24小时内达到79%),并通过即时药物释放快速止血(60秒内达到92%)。最重要的是,体内研究表明,MNs-D通过在磁导航下插入胃黏膜层,克服了传统口服疗法中令人不安的胃黏膜屏障,从而实现抗生素的持续释放以长期根除幽门螺杆菌(99%)。对于针对胃幽门螺杆菌感染的不同双模式药物释放,本研究可能首次考察了口服磁导航微针的效果。

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