Journal of controlled release : official journal of the Controlled Release Society · 2025
The pharmacokinetic profile of mitomycin C released from an injectable supramolecular hydrogel in a rodent model.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wintjens Anne G W E, Fransen Peter-Paul K H, Lenaerts Kaatje, Liu Hong, van Almen Geert C, Gijbels Marion J, Janssen Ben J A, de Hingh Ignace H J T, Dankers Patricia Y W, Van Der Speeten Kurt, Bouvy Nicole D, Marchal Wouter
Аннотация
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.
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.