3D-printed dual-actuation drug delivery device combining continuous perfusion and iontophoresis

Tumours exhibit substantial inter- and intra-patient heterogeneity, including differences in geometric dimensions and tissue stiffness, making the development of one-size-fits-all local drug delivery systems (DDSs) challenging. Herein, we investigate a novel 3D-printed DDS designed to provide adaptable device geometry and greater control over drug release. The system integrates continuous perfusion with iontophoretic delivery, enabling both maintenance of the drug reservoir and externally controlled transport. The combined delivery strategy was investigated over 400 min using an in vitro phantom model, with machine vision employed to monitor drug release in real time. A design of experiments (DoE) approach was used to systematically investigate the influence of key device and operating parameters on drug release. Membrane area, applied voltage and drug concentration were found to significantly affect drug release, whereas flow rate did not. Subsequent physics-based modelling indicated that the device geometry induced pressure and velocity losses that limited the influence of flow rate on drug transport. Nevertheless, continuous perfusion served to replenish the drug reservoir, counteracting the progressive depletion of the concentration gradient observed during passive release. These findings indicate that, within the investigated design, iontophoresis provides the primary externally tuneable mechanism for controlling drug release, while continuous perfusion maintains reservoir conditions. As 3D printing is an emerging technology in pharmaceutical manufacturing, the mechanical performance of the printed material was also investigated under physiologically relevant conditions. Although scanning electron microscopy provided no evidence of morphological degradation, mechanical testing demonstrated a reduction in material strength following exposure to 37 °C and bio-relevant media, warranting further investigation. Overall, the study demonstrates the potential of 3D printing to realise dual-actuation drug delivery, in which continuous perfusion maintains reservoir conditions while iontophoresis provides externally tunable control over drug transport. The findings provide a foundation for the development of more adaptable and sophisticated 3D-printed DDSs.