Computational simulations of localized injection of a PH-sensitive hydrogel for intraperitoneal drug delivery

Peritoneal metastasis is associated with poor prognosis and severely compromised quality of life. In addition to surgery and systemic therapy, intraperitoneal (IP) drug delivery has emerged as a promising treatment option. However, most current chemotherapy drugs have a low molecular weight, and are rapidly cleared from the peritoneal cavity. However, administration in hydrogel form prolongs IP residence time and may enhance anticancer efficacy. Here, we used multi-physics simulations to assess how injection flow rate, gelation time, post-gelation viscosity, and acidosis influence the distribution of a pH-sensitive hydrogel within a peritoneal cavity. A 3D elliptical cavity was modeled in COMSOL Multiphysics. Ureidopyrimidone-poly (ethylene glycol) (UPy-PEG) was modeled as an injectable hydrogel, which remains liquid at pH 9 but undergoes a sol-gel transition upon contact with the peritoneum (pH 7.4). To accurately capture this behavior, multi-physics simulations were conducted by coupling fluid flow, transport of diluted species, and multiphase interactions that simulate an identical volume of hydrogel administered at different flow rates and viscosity profiles. The results illustrate how the injection parameters modify the pH distribution. A low flow rate prolongs the filling process, resulting in an inhomogeneous hydrogel distribution. In contrast, a high flow rate ensures more complete coverage. The gelation time and post-gelation viscosity affect both hydrogel distribution and the fraction that remains at elevated pH. Acidosis rapidly lowers pH. This computational study highlights the importance of an adequate flow rate and tuning the hydrogel properties when IP administering a pH-sensitive hydrogel.