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

Anne G. W. E. Wintjens; Peter-Paul K. H. Fransen; Kaatje Lenaerts; Hong Liu; Geert C. van Almen; Marion J. Gijbels; Ben J. A. Janssen; Ignace H. J. T. de Hingh; Patricia Y. W. Dankers; Kurt van der Speeten; Nicole D. Bouvy; Wouter Marchal

doi:10.1016/j.jconrel.2025.113763

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

Anne G. W. E. Wintjens
, Peter-Paul K. H. Fransen
, Kaatje Lenaerts
, Hong Liu
, Geert C. van Almen
, Marion J. Gijbels
, Ben J. A. Janssen
, Ignace H. J. T. de Hingh
, Patricia Y. W. Dankers
, Kurt van der Speeten
, Nicole D. Bouvy^*
, Wouter Marchal

^*Corresponding author for this work

Medical Biochemistry

Maastricht University
UPyTher BV
Eindhoven University of Technology
Amsterdam UMC
Catharina Hospital
Transnationale Universiteit Limburg
East Limburg Hospital

Research output: Contribution to journal › Article › Academic › peer-review

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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 pbs-MMC (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 ± 21 μg/L and a Tmax of 52.5 ± 8.2 min; pbs-MMC had a Cmax of 358 ± 24 μg/L and a Tmax of 37.5 ± 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.

Original language	English
Article number	113763
Journal	Journal of controlled release
Volume	383
DOIs	https://doi.org/10.1016/j.jconrel.2025.113763
Publication status	Published - 10 Jul 2025

Keywords

Drug delivery system
LC-ESI-MS
Mitomycin C
Pharmacokinetics
UPy-PEG

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Wintjens, A. G. W. E., Fransen, P.-P. K. H., Lenaerts, K., Liu, H., van Almen, G. C., Gijbels, M. J., Janssen, B. J. A., de Hingh, I. H. J. T., Dankers, P. Y. W., van der Speeten, K., Bouvy, N. D., & Marchal, W. (2025). The pharmacokinetic profile of mitomycin C released from an injectable supramolecular hydrogel in a rodent model. Journal of controlled release, 383, Article 113763. https://doi.org/10.1016/j.jconrel.2025.113763

@article{d3de0aba93f84944a542974ee4cd3f61,

title = "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 pbs-MMC (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 ± 21 μg/L and a Tmax of 52.5 ± 8.2 min; pbs-MMC had a Cmax of 358 ± 24 μg/L and a Tmax of 37.5 ± 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.",

keywords = "Drug delivery system, LC-ESI-MS, Mitomycin C, Pharmacokinetics, UPy-PEG",

author = "Wintjens, \{Anne G. W. E.\} and Fransen, \{Peter-Paul K. H.\} and Kaatje Lenaerts and Hong Liu and \{van Almen\}, \{Geert C.\} and Gijbels, \{Marion J.\} and Janssen, \{Ben J. A.\} and \{de Hingh\}, \{Ignace H. J. T.\} and Dankers, \{Patricia Y. W.\} and \{van der Speeten\}, Kurt and Bouvy, \{Nicole D.\} and Wouter Marchal",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = jul,

day = "10",

doi = "10.1016/j.jconrel.2025.113763",

language = "English",

volume = "383",

journal = "Journal of controlled release",

issn = "0168-3659",

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Wintjens, AGWE, Fransen, P-PKH, Lenaerts, K, Liu, H, van Almen, GC, Gijbels, MJ, Janssen, BJA, de Hingh, IHJT, Dankers, PYW, van der Speeten, K, Bouvy, ND & Marchal, W 2025, 'The pharmacokinetic profile of mitomycin C released from an injectable supramolecular hydrogel in a rodent model', Journal of controlled release, vol. 383, 113763. https://doi.org/10.1016/j.jconrel.2025.113763

TY - JOUR

T1 - The pharmacokinetic profile of mitomycin C released from an injectable supramolecular hydrogel in a rodent model

AU - Wintjens, Anne G. W. E.

AU - Fransen, Peter-Paul K. H.

AU - Lenaerts, Kaatje

AU - Liu, Hong

AU - van Almen, Geert C.

AU - Gijbels, Marion J.

AU - Janssen, Ben J. A.

AU - de Hingh, Ignace H. J. T.

AU - Dankers, Patricia Y. W.

AU - van der Speeten, Kurt

AU - Bouvy, Nicole D.

AU - Marchal, Wouter

PY - 2025/7/10

Y1 - 2025/7/10

N2 - 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 pbs-MMC (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 ± 21 μg/L and a Tmax of 52.5 ± 8.2 min; pbs-MMC had a Cmax of 358 ± 24 μg/L and a Tmax of 37.5 ± 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.

AB - 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 pbs-MMC (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 ± 21 μg/L and a Tmax of 52.5 ± 8.2 min; pbs-MMC had a Cmax of 358 ± 24 μg/L and a Tmax of 37.5 ± 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.

KW - Drug delivery system

KW - LC-ESI-MS

KW - Mitomycin C

KW - Pharmacokinetics

KW - UPy-PEG

UR - https://www.scopus.com/pages/publications/105003413039

U2 - 10.1016/j.jconrel.2025.113763

DO - 10.1016/j.jconrel.2025.113763

M3 - Article

C2 - 40274069

SN - 0168-3659

VL - 383

JO - Journal of controlled release

JF - Journal of controlled release

M1 - 113763

ER -

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

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Keywords

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