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Selective delivery of 5-fluorouracil (5-FU) to i.p. tissues using 5-FU microspheres in rats
A Hagiwara1, C Sakakura, H Tsujimoto
1First Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Japan.
Abstract:
A new formulation has been developed for the delivery of 5-fluorouracil (5-FU) in treating peritoneal carcinomatosis. The new formulation (5-FU-MS) involves the incorporation of 5-FU into microspheres composed of a poly(glycolide-co-lactide) matrix. The incorporated 5-FU is released slowly over a 3 week period. We investigated the drug distribution and pharmacokinetics of 5-FU in rats receiving an i.p. injection of 5-FU-MS or aqueous 5-FU solution. The concentration of 5-FU was higher in the i.p. tissues (omentum and mesentery) and lower in the extraperitoneal tissues (blood plasma, lung and heart) in rats given 5-FU-MS than in rats given the aqueous 5-FU solution. Pharmacokinetic analysis showed that the area under the curve (AUC) was significantly greater in the omentum and the mesentery than in other tissues of rats given 5-FU-MS. There was no significant difference in the AUC in the tissues of rats given the aqueous 5-FU solution.
Insights
A novel 5-fluorouracil (5-FU) microsphere formulation enhances drug delivery for peritoneal carcinomatosis. This formulation increases 5-FU concentration in targeted tissues, improving treatment efficacy.
Area of Science:
- Oncology
- Pharmaceutics
- Drug Delivery Systems
Background:
- Peritoneal carcinomatosis presents challenges for effective chemotherapy delivery.
- Conventional 5-fluorouracil (5-FU) administration may lead to suboptimal drug concentrations at the tumor site.
- Developing targeted drug delivery systems is crucial for improving treatment outcomes.
Purpose of the Study:
- To evaluate a new 5-fluorouracil-loaded microsphere (5-FU-MS) formulation for peritoneal carcinomatosis treatment.
- To investigate the drug distribution and pharmacokinetics of 5-FU-MS compared to aqueous 5-FU solution.
- To assess the potential of 5-FU-MS for localized and sustained drug release.
Main Methods:
- Development of 5-FU-MS using a poly(glycolide-co-lactide) matrix for slow release over 3 weeks.
- Intraperitoneal (i.p.) administration of 5-FU-MS and aqueous 5-FU solution in a rat model.
- Measurement of 5-FU concentrations in various peritoneal and extraperitoneal tissues.
- Pharmacokinetic analysis, including calculation of the area under the curve (AUC).
Main Results:
- 5-FU-MS resulted in significantly higher 5-FU concentrations in intraperitoneal tissues (omentum, mesentery) compared to aqueous 5-FU.
- Conversely, 5-FU-MS led to lower 5-FU concentrations in extraperitoneal tissues (blood plasma, lung, heart).
- Pharmacokinetic analysis revealed a significantly greater AUC in the omentum and mesentery for 5-FU-MS, indicating sustained local drug exposure.
Conclusions:
- The novel 5-FU-MS formulation demonstrates improved drug distribution for peritoneal carcinomatosis.
- Sustained release and enhanced local concentration of 5-FU in target tissues are key benefits.
- This formulation holds promise for more effective and targeted chemotherapy in peritoneal carcinomatosis.