The pharmacokinetic profile of mitomycin C released from an injectable supramolecular hydrogel in a rodent model

Abstract

Objective: This study evaluates the pharmacokinetics of an ureido-pyrimidinone poly(ethylene) glycol (UPy-PEG) hydrogel loaded with mitomycin C (MMC) in rats. The hydrogel aims to enhance the intraperitoneal residence time of MMC, potentially improving therapeutic outcomes for peritoneal metastases (PM) patients. Methods: Rats were divided into two groups: h-MMC (n = 8), receiving MMC encapsulated in hydrogel, and pbsMMC (n = 6), receiving MMC in PBS. Blood samples were collected from 5 min to 48 h post-administration. MMC concentrations were measured using LC-ESI-MS. Systemic and local adverse effects were assessed through blood analysis and post-mortem histopathology. Results: The hydrogel prolonged detectable plasma MMC levels: 24 h for h-MMC vs. 4 h for pbs-MMC. h-MMC had a Cmax of 120 f 21 mu g/L and a Tmax of 52.5 f 8.2 min; pbs-MMC had a Cmax of 358 f 24 mu g/L and a Tmax of 37.5 f 8.2 min. The area under the curve ratio of h-MMC/pbs-MMC was 87 %. Platelet counts were significantly lower in h-MMC at 24- and 48 h and in pbs-MMC at 48 h. No liver or kidney damage was observed, though vacuolated macrophages were noted in the hydrogel-treated groups. Conclusion: The hydrogel effectively prolonged MMC presence in plasma, suggesting extended intraperitoneal residence time and supporting previous findings of therapeutic effectiveness in a PM rat model.