Modeling and ex vivo evaluation of electrostatic precipitation-enhanced intraperitoneal aerosol drug delivery

Peritoneal metastases (PM) remain a significant clinical challenge due to their resistance to systemic chemotherapy. Intraperitoneal aerosolized drug delivery (IPADD) has shown promise as a localized treatment option; however, its efficacy is often limited by inadequate aerosol droplet distribution and poor tissue penetration. In this study, we enhance IPADD using electrostatic precipitation (eIPADD) and evaluate its performance through computational simulations and in vitro/ex vivo experiments. A realistic 3D reconstruction of the human peritoneal cavity was used to simulate the effects of electrostatic fields on droplet distribution and deposition. The results demonstrated that multiple electrodes improved aerosol homogeneity and tissue penetration depth. These findings were validated in vitro, where eIPADD significantly increased droplet coverage and tissue penetration, particularly in anatomically challenging regions. Importantly, increasing the number of electrodes from one to three further enhanced droplet distribution uniformity and tissue penetration depth. While raising the electrical potential improved deposition in key areas, benefits plateaued beyond 10 kV, suggesting a threshold in efficacy. Nevertheless, optimizing voltage within this range, in conjunction with the increased electrode count, remains critical for achieving consistent drug delivery across the peritoneal surfaces and maximizing therapeutic outcomes. Our findings suggest that eIPADD has the potential to address the limitations of conventional IPADD, providing a more effective and uniform drug delivery method for treating PM.