Fabrication and characterization of a multilayered membrane for biliary stents enabling directional delivery of UDCA and aspirin

Abstract Biliary obstruction prevents normal flow of bile into the duodenum, resulting in the accumulation of hydrophobic bile acids. This causes oxidative stress and subsequent hepatocellular injury. Although biliary stents are commonly used to restore bile flow, their long-term patency is often limited by the risk of restenosis. Ursodeoxycholic acid (UDCA) is widely used to treat cholelithiasis; however, its incorporation into stent-based delivery systems has not been extensively studied. To address this issue, we designed a UDCA-based multilayer drug-eluting membrane for biliary stents to restore bile flow. It comprises an inner UDCA-loaded polycaprolactone (PCL) layer, a central silicone barrier film, and an outer aspirin-loaded PCL layer. The central silicone film provides structural integrity and enables directional drug release, allowing the inward diffusion of UDCA and the outward release of aspirin. UDCA in the inner layer prevents bio-sludge formation within the bile ducts, whereas aspirin in the outer layer helps reduce local inflammation at the stent insertion site. The physicochemical and mechanical properties of the membranes were characterized, and their biocompatibility was evaluated. Aspirin release kinetics were measured using UV spectrophotometry. UDCA release was indirectly assessed based on its regenerative effects in HepG2 cells under oxidative stress, including NRF2 and HO-1 gene expression analysis, using quantitative RT-PCR. The multilayered drug-eluting membrane demonstrated enhanced mechanical strength and enabled sustained directional drug release with a reduced initial burst. These findings suggest that the multilayered drug-eluting membrane holds potential as a platform for localized and controlled drug delivery while addressing the key mechanical and therapeutic limitations of current stents.