Silk-based double-sided magnetic microneedles for enhanced targeted retention in the gastrointestinal tract

Gastrointestinal-retentive drug delivery devices represent a novel oral drug delivery approach capable of significantly enhancing patient compliance and improving local drug delivery efficiency compared to conventional oral formulations. However, developing gastrointestinal-retentive drug delivery devices with high retention capability based on compatible material systems presents significant challenges. Here, we introduce silk-based double-sided magnetic microneedles (SDMMs) designed to facilitate targeted oral drug delivery with precise local retention in the gastrointestinal tract. The SDMM platform demonstrates robust mechanical properties, site-specific degradation, and compatibility with various capsule geometries, facilitating seamless integration into existing oral delivery systems. In vitro analyses demonstrate region-dependent drug release from the SDMM platform, supporting its potential for localized delivery of drugs in the gastrointestinal tract. The incorporation of iron oxide nanoparticles (IONPs) confers magnetically responsive targeting, offering a significant advantage over conventional approaches by ensuring precise retention and enhancing the targeted delivery potential under external magnetic fields. Notably, SDMMs retain their positions under fluid flow rates up to 550 mL min^-1 (stomach) and 400 mL min^-1 (small intestine), respectively, underscoring their superior gastrointestinal retention. Furthermore, in vivo retention experiments also showed significantly enhanced retention in the gastrointestinal tract, with the retention time of SDMMs reaching almost 15 hours with magnet assistance, representing significantly prolonged retention compared to typical transit times in these regions. These findings establish SDMMs as a promising platform for precise, efficient, and patient-friendly oral drug delivery.