Organ distribution of 5-fluorouracil loaded gelatine microspheres in mice
Xiuhua Hao1, Gang Cheng, Meijuan Zou
1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Abstract:
The aim of this study was to investigate the organ distribution characteristics of 5-fluorouracil (5-Fu) loaded crosslinked gelatine microspheres (5-Fu-MS) after intravenous (i.v.) injection compared to 5-Fu solution in mice, and to evaluate the targetability of 5-Fu-MS. The concentrations of 5-Fu in mice plasma, heart, liver, lung, kidney, spleen and brain were determined by HPLC. The parameters drug targeting index C(e), time-averaged relative drug exposure values r(e), drug targeting efficiency t(e), and drug distributed to target-tissue (%) were used to evaluate the targetability of the 5-Fu-MS delivery system. The results showed that the concentration of 5-Fu in the lung was significantly higher than after application of 5-Fu solution, and that the maximum concentration of 5-Fu, 72.8 microg x g organ(-1), was reached in the lung at 15 min after i.v. administration. As for 5-Fu-MS, r(e) was calculated to be 2.2, and t(e) was considerably higher than after application of 5-Fu in solution. Furthermore, the percentage of drug distributed to the lung was 2 times as high as after application in solution. Accordingly, 5-Fu-MS were capable of effectively delivering 5-Fu to the lung and possessed specific targetability towards the lung compared to 5-Fu solution.
Insights
Crosslinked gelatin microspheres effectively delivered 5-fluorouracil (5-Fu) to the lungs in mice. This novel 5-Fu loaded microsphere (5-Fu-MS) system demonstrated superior lung targeting compared to 5-Fu solution.
Area of Science:
- Pharmacology
- Biomedical Engineering
- Drug Delivery Systems
Background:
- 5-fluorouracil (5-Fu) is a chemotherapy drug with limited targeted delivery.
- Developing effective drug delivery systems is crucial for improving cancer treatment efficacy and reducing side effects.
Purpose of the Study:
- To investigate the organ distribution of 5-fluorouracil (5-Fu) loaded crosslinked gelatin microspheres (5-Fu-MS) after intravenous injection in mice.
- To compare the targetability of 5-Fu-MS with 5-Fu solution for enhanced lung delivery.
Main Methods:
- Intravenous administration of 5-Fu-MS and 5-Fu solution to mice.
- Quantification of 5-Fu concentrations in various organs (plasma, heart, liver, lung, kidney, spleen, brain) using High-Performance Liquid Chromatography (HPLC).
- Evaluation of drug targeting parameters including drug targeting index, relative drug exposure, drug targeting efficiency, and percentage of drug distributed to target tissue.
Main Results:
- 5-Fu-MS significantly increased 5-Fu concentration in the lung compared to 5-Fu solution.
- Maximum 5-Fu concentration in the lung (72.8 microg/g) was achieved at 15 minutes post-injection of 5-Fu-MS.
- The time-averaged relative drug exposure (r(e)) was 2.2, and drug targeting efficiency (t(e)) was considerably higher for 5-Fu-MS.
- The percentage of drug distributed to the lung was twofold higher with 5-Fu-MS compared to the solution.
Conclusions:
- 5-Fu-MS demonstrate effective delivery of 5-fluorouracil to the lung.
- The crosslinked gelatin microsphere system exhibits specific targetability towards the lung.
- This targeted delivery approach holds promise for improving lung cancer chemotherapy.
