Multimodal Magnetic, Photothermal, Ultrasonic, and Vibrational Actuation of Drug-Loaded Superparamagnetic Iron Oxide Nanoparticles for Enhanced Transport Across Semipermeable Membranes

The round window membrane (RWM) presents a major barrier to local drug delivery into the inner ear. Although magnetically guided superparamagnetic iron oxide nanoparticles (SPIONs) have shown promise for enhancing transport across the RWM, the effectiveness of magnetic-field-driven delivery decreases rapidly with distance from the magnet, limiting clinical applicability. In this study, PEGylated SPIONs were investigated as externally actuated carriers for enhanced transport across membrane barriers using magnetic, photothermal, ultrasonic, and vibrational stimulation. Nanoparticle transport was evaluated using a custom dual-chamber benchtop platform containing porcine small intestinal submucosa (SIS) membranes as a model transport barrier. Transport studies demonstrated that magnetic-field-assisted delivery significantly increased magnetic nanoparticle (MNP) transport rates relative to passive diffusion; however, transport enhancement decreased sharply with increasing magnet-to-membrane distance. To overcome this limitation, alternative external actuation strategies were explored. Laser-induced photothermal heating, ultrasonication, and mechanical vibration all significantly enhanced MNP transport, even in the absence of magnetic fields. Among the conditions examined, combined magnetic and photothermal stimulation produced the highest transport rates, indicating synergistic enhancement. These results show that MNP transport can be effectively enhanced through magnetic, thermal, and mechanical mechanisms. The findings establish a multimodal transport-engineering framework for improving drug delivery across the RWM and suggest clinically translatable alternatives to magnetic-field-only approaches for inner-ear therapy.