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

Localized drug delivery to solid tumors using implantable or locally applied drug delivery system (DDS) is constrained by limited adaptability to patient- and lesion-specific transport conditions (e.g., tumor geometry and local microenvironment), necessitating the need for novel DDS. Herein, we investigated the potential of three-dimensional (3D) printing to fabricate a dual-actuation DDS combining continuous perfusion with iontophoretic delivery. The rationale was to leverage 3D printing for geometry personalization (e.g., contact area/reservoir dimensions) and to enable continuous perfusion for reservoir replenishment, while iontophoresis provides programmable modulation of transport via externally applied voltage. A design of experiments (DoE) approach was implemented to systematically identify the critical process parameters influencing drug release. Furthermore, calibrated time-lapse imaging with image binarization and segmentation was used to monitor the continuous in vitro drug-release in real-time. The analysis revealed that membrane area, voltage and drug concentration were statistically significant in influencing drug release, whereas flow rate was found to be statistically insignificant, which suggests that continuous perfusion primarily supports reservoir replenishment rather than serving as a dominant control of release rate in the current configuration. Subsequent computational fluid dynamics suggested that the device geometry induces a pressure and velocity drop within the reservoir region, which is consistent with the observed flow-rate insensitivity. Moreover, externally applied voltage was identified in this study as a pivotal control parameter, enabling programmable modulation of transport kinetics for the charged model molecule. The mechanical properties of the 3D printed device were also evaluated, where a mechanical susceptibility to 37 °C and saline was seen, which necessitates rigorous assessment of 3D printing materials under physiologically relevant conditions. The study supports the use of 3D printing to realize dual-actuation delivery in which continuous perfusion maintains reservoir conditions while iontophoresis provides the primary externally tunable control of transport, further advancing the utility of pharmaceutical 3D printing. The research lays the groundwork for more sophisticated DDS development using 3D printing.