Core-shell floating hydrogel assembly for sustained dual-drug delivery and ultrasound imaging in rheumatoid arthritis

A hydrogel assembly was developed for the sustained delivery of hydrophilic and hydrophobic drugs. • The hydrogel assembly was able to provide sustained drug release. • The CO₂ bubbles within the hydrogel provided ultrasound imaging signals. Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by sustained joint inflammation and prolonged pain. Conventional oral combination therapy often suffers from mismatched release profiles of hydrophilic and hydrophobic drugs and lacks real-time monitoring capability. To address these challenges, we developed a gastric-floating core-shell hydrogel assembly for the sustained co-delivery of acetaminophen (APAP) and methotrexate (MTX). The poly(vinyl alcohol) (PVA) core encapsulates the analgesic APAP, while the silk fibroin (SF) shell, featuring methanol-induced β-sheet structures, carries the anti-inflammatory MTX. This spatial compartmentalization enables independent control over the release profiles of the two drugs. Sodium bicarbonate embedded in the shell reacts with gastric acid to generate CO₂ bubbles, which are stably retained by the dense β-sheet network, conferring buoyancy for up to 48 h. Notably, these retained CO₂ bubbles serve as intrinsic ultrasound contrast agents, enabling real-time imaging of gastric retention without the need for exogenous contrast agents. In vitro drug release studies demonstrate sustained release of both APAP and MTX. This integrated platform combines spatially compartmentalized dual-drug delivery, prolonged gastric retention, and non-invasive monitoring, offering a promising strategy for oral RA therapy. Download: Download high-res image (229KB) Download: Download full-size image